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Information on EC 3.4.24.B17 - FtsH endopeptidase and Organism(s) Escherichia coli and UniProt Accession P0AAI3
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3.4.24.B17 FtsH endopeptidaseSpecify your search results
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
t.ftsh, mtftsh, cell division protein ftsh, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
FtsH
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolytic degradation of proteins
degenerate cleavage specificity, degradation of hydrophobic membrane-spanning segments of misfolded mitochodrial membrane proteins
-
proteolytic degradation of proteins
degradation of soluble and integral membrane proteins
-
proteolytic degradation of proteins
enzyme is a AAA protease, highly conserved residues Phe228 and Gly230 lie in the central pore region of the hexamer and are important in proteolysis and coupling to ATP
-
proteolytic degradation of proteins
essential for activity are residues Asn301, Asp307, Arg312, and Arg315, mechanism, ligand binding site at residues 144-398
-
proteolytic degradation of proteins
mechanism, reaction only occurs with protein substrates of low intrinsic thermodynamic stability, sequential degradation from the tail
-
proteolytic degradation of proteins
preference for positively charged and hydrophobic amino acid residues, large cytoplasmic domain contains ATPase and protease activities
-
proteolytic degradation of proteins
the second transmembrane segment participates in not only its membrane-anchoring, but also its protease activity and homolgomerization, it is located next to the C-terminal cytoplasmic region of the enzyme
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
171904-23-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-deoxy-D-manno-octulosonate transferase + H2O
?
3-deoxy-D-manno-octulosonate transferase carries out the attachment of two KDO residues to the lipid A precursor (lipid IVA) to form the minimal essential structure of the lipopolysaccharide (KDO2-lipid A). Thus, FtsH regulates the concentration of the lipid moiety of LPS (lipid A) as well as the sugar moiety (KDO-based core oligosaccharides), ensuring a balanced synthesis of lipopolysaccharide
-
-
?
heat shock sigma factor RpoH (sigma32) + H2O
?
in addition to the turnover element in region 2.1, a second region important for proteolysis of RpoH by FtsH lies in region C of the sigma factor
-
-
?
protein GlpG + H2O
?
helical bundle membrane protein, model membrane substrate
-
-
?
unstable derivatives of the N-terminal domain of the lambdacI repressor + H2O
?
3 derivatives with a nonpolar pentapeptide tail, i.e. cI104, cI105, cI108, and 1 with the SsrAtag, i.e. cI-SsrA
-
?
apo-flavodoxin + H2O
?
-
degradation of apo-flavodoxin from Escherichia coli, no degradation of holo-flavodoxin containing non-covalently bound flavin mononucleotide. A mutant flavodoxin carrying a substitution of Tyr94 to Asp (FldYD) with a lower affinity for FMN is efficiently degraded. FtsH is able to initiate degradation of the FldYD moiety even when it is sandwiched by glutathione S-transferase, green fluorescent protein, or both green fluorescent protein and glutathione S-transferase
-
-
?
barnase tagged with SsrA tail + H2O
?
-
tail specific degradation
-
?
beta-casein + H2O
small peptides of 13-20 amino acid residues
-
-
product analysis
?
chimeric protein PhoA-TM8-C30 + H2O
?
-
recombinant substrate protein consists of one transmembrane segment of protein SecY, i.e. TM8, plus the following 30 residues of a cytoplasmic part, and the C-terminal end of alkaline phosphatase PhoA
-
?
dihydrofolate reductase tagged with SsrA tail + H2O
?
-
tail specific degradation
-
?
FGH-(NO2)FFAF-methyl ester + H2O
FGH-(NO2)F + Phe-Ala-Phe-methyl ester
-
exclusively cleaved at the (NO2)Phe-Phe bond
-
?
flavodoxin + H2O
?
-
degrades flavin mononucleotide-free flavodoxin but not holo-flavodoxin
-
-
?
fusion protein SecY-(P5)-PhoA + H2O
?
-
recombinant substrate protein consists of one protein SecY without its C-terminus, and the alkaline phosphatase PhoA
-
?
lambda Xis + H2O
?
-
protein substrate is required for site-specific excision of phage lambda from the bacterial chromosome
-
?
phage lambda CII protein + H2O
small peptides
-
enzyme participates in the phage lambda lysis-lysogeny decision by degrading the CII transcriptional activator and by its response to inhibition by the lambda CIII gene product
-
?
phage lambda CII protein + H2O
small peptides of 13-20 amino acid residues
-
recombinant protein substrate with -terminal or C-terminal His-tag, respectively, or no His-tag
product analysis
?
phage shock protein C + H2O
?
-
phage shock protein C is the only core component of the phage shock protein system affected by FtsH. Phage shock protein B prevents FtsH-dependent degradation of phage shock protein C
-
-
?
protein P22 Arc repressor tagged with 108 motif tail + H2O
?
-
tail specific degradation
-
?
protein P22 Arc repressor tagged with SsrA tail + H2O
?
-
tail specific degradation
-
?
protein sigma32 + H2O
peptides
-
regulatory protein
approximately 10 peptides with MW below 3 kDa
?
RpoH protein + H2O
?
-
enzyme recognizes the internal RpoH protein region, N- and C-terminus have no or only marginal effect on substrate binding
-
?
ssrA-tagged ProW1-182 + H2O
?
substrate is a truncated variant of multiple-pass inner-membrane protein ProW
-
-
?
UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase + H2O
?
-
-
-
-
?
uncomplexed form of the subunit alpha of the proton ATPase F0 + H2O
?
-
-
-
-
?
protein + H2O
peptides
tail specific pathway for removing abnormal cytoplasmic proteins via the enzyme, disposition by degradation of polypeptides synthesized from truncated mRNA molecules and are C-terminally tagged with an 11-amino-acid nonpolar destabilizing tail via a mechanism involving the 10Sa stable RNA
-
?
LpxC + H2O
?
-
ATP-dependent. Essentiality of FtsH lies in its function to keep the proper LPS/phospholipid ratio by degrading LpxC
-
-
?
Protein + H2O
?
-
FtsH degrades misassembled membrane proteins and a subset of cytoplasmic regulatory proteins
-
-
?
Protein + H2O
?
-
the enzyme can unfold proteins with lower Tms such as glutathione S-transferase (Tm: 52°C)
-
-
?
protein + H2O
peptides
-
ATP hydrolysis cause conformational changes, regulate the accessibility of the proteolytic sites and trigger unfolding of substrate polypeptides, C-terminally located second region of homology, i.e. SRH region, is conserved throughout the AAA proteases and plays an intermolecular catalytic role
-
?
protein + H2O
peptides
-
degradation of membrane and cytoplasmic proteins
-
?
protein + H2O
peptides
-
degradation probably involves dislocation of the substrate membrane protein to the cytosol
-
?
protein + H2O
peptides
-
enzyme recognizes nonpolar tails, overview, degrades integral and cytoplasmic proteins
-
?
protein + H2O
peptides
-
enzyme shows limited substrate specificity which is not primarily determined by the structure of the protein
-
?
protein + H2O
peptides
-
preference for positively charged and hydrophobic amino acid residues, degradation of uncomplexed integral membrane proteins and short-life cytoplasmic proteins
-
?
protein + H2O
peptides
-
substrate binding by the cytoplasmic domain
-
?
protein + H2O
peptides
-
substrate specificity, soluble and integral membrane proteins, initiation of degradation by recognition and binding of more than 20 amino acids of the C-terminal cytosolic tail of the substrate, subsequently the substrate can be dislocated into the cytosol or degraded simultaneously bidirectionally
-
?
protein + H2O
peptides
-
degradation of regulatory proteins to control gene activity and metabolism
-
?
protein + H2O
peptides
-
degrades misassembled membrane protein complexes and plays a vital role in membrane quality control, degrades cytoplasmic regulatory proteins
-
?
protein + H2O
peptides
-
enzyme affects several processes including cell division, the synthesis of phospholipids and lipopolysaccharides, the anchoring of integral membrane proteins, mRNA stability, and colchicin tolerance, degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein + H2O
peptides
-
housekeeping function, because the enzyme lacks a robust unfoldase activity, it is able to use the substrate protein folding state as a criterion for degradation
-
?
protein + H2O
peptides
-
involved in membrane protein assembly as well as degradation of unstable proteins
-
?
protein + H2O
peptides
-
involved in the degradation of regulatory proteins and uncomplexed subunits of membrane protein complexes
-
?
protein + H2O
peptides
-
FtsH degrades a set of short-lived proteins, enabling cellular regulation at the level of protein stability. FtsH also degrades some misassembles membrane proteins, contributing to their quality maintenance. One biological role of FtsH might be to affect the development and life cycle of infecting or episomal genetic systems, by degrading their key regulatory molecules. The enzyme has a special ability to dislocate membrane protein substrates out of the membrane for which its own membrane-embedded nature is essential
-
-
?
protein F0 subunit a + H2O
?
-
subunit a of the F0 part of the H+-ATPase, unstable in the absence of other F0 subunits leading to degradation by the enzyme
-
?
protein F0 subunit a + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
protein LpxC + H2O
?
-
essential for cell viability, enzyme controls the steady-state level of the LpxC protein, which has a key regulatory role in the biosynthesis of lipopolysaccharides
-
?
protein LpxC + H2O
?
-
protein LpxC is UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase
-
-
?
protein LpxC + H2O
?
-
turnover of LpxC requires a length- and sequence-specific C-terminal degradation signal. LpxC proteins from Salmonella enterica, Yersinia pseudotuberculosis, and Vibrio cholerae are degraded with half-lives comparable to the half-life of Escherichia coli LpxC (8 to 12 min). LpxC from Pseudomonas aeruginosa is degraded slowly with a half-life of 78 min. LpxC proteins from Agrobacterium tumefaciens and Rhodobacter capsulatus are degraded with half-lives of about 68 min and 20 min, respectively
-
-
?
protein SecY + H2O
?
-
substrate protein is a subunit of protein translocase, failed to assemble with its partner SecE
-
?
protein SecY + H2O
?
-
uncomplexed subunit of the protein translocase
-
?
protein SecY + H2O
?
-
uncomplexed subunit of the protein translocase
-
?
protein SecY + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
protein SecY + H2O
?
-
quality control, the enzyme regulates the amount of SecY assembled in the mitochondrial membrane, elimination of uncomplexed SecY is important for optimum protein translocation and for the integrity of the membrane
-
?
protein SecY + H2O
?
-
SecY protein is a subunit of protein translocase
-
?
protein sigma32 + H2O
?
-
no activity with the isolated 21 amino acid peptide from the C-terminus, heat shock promotor-specific subunit of RNA polymerase, wild-type and C-terminally truncated, up to 21 amino acid residues, protein, the substrates C-terminus is not required for activity or recognition and binding
-
?
protein sigma32 + H2O
?
-
wild-type enzyme and fusion mutants MF1-4, not MF5, substrate protein is a heat-shock transcription factor, sigma32-C-his
-
?
protein YccA + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
sigma32 + H2O
?
-
hydrolyzes about 140 ATP molecules during the degradation of a single molecule of cy2-sigma32. Degradation of sigma32 proceeds from the N-terminus to the C-terminus
-
-
?
additional information
?
-
enzyme shows overlapping substrate specificity with the proteases C1pXP and C1pAP, the enzymes can compensate for each other in degrading the c1-SsrA tagged substrate protein
-
?
additional information
?
-
FtsH functions as a membrane chaperone and protease. FtsH and YidC have a linked role in the quality control of inner membrane proteins
-
-
?
additional information
?
-
-
no activity with bovine serum albumin
-
?
additional information
?
-
-
construction of an in vitro reaction system in which the enzyme is membrane embedded and not solubilized by detergent, two inverted membrane vesicles or proteoliposomes, one bearing the enzyme, the other bearing the substrate protein, are fused
-
?
additional information
?
-
-
large complexes exhibit either ATPase and protease activity, while smaller ones do not
-
?
additional information
?
-
-
no activity with GFP-tagged proteins
-
?
additional information
?
-
-
the enzyme acts in cooperation with the homologous proteins HflK and HflC, the 3 proteins assemble at the periplasmic site of the plasma membrane, resulting in prohibitin-like modulation of the enzymes substrate specificity and activity
-
?
additional information
?
-
-
dislocation of membrane proteins mediated by the enzyme, periplasmic segments can also be degraded by the enzyme
-
?
additional information
?
-
-
protein LpxC from A aeolicus is not degraded by FtsH from Escherichia coli
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-deoxy-D-manno-octulosonate transferase + H2O
?
3-deoxy-D-manno-octulosonate transferase carries out the attachment of two KDO residues to the lipid A precursor (lipid IVA) to form the minimal essential structure of the lipopolysaccharide (KDO2-lipid A). Thus, FtsH regulates the concentration of the lipid moiety of LPS (lipid A) as well as the sugar moiety (KDO-based core oligosaccharides), ensuring a balanced synthesis of lipopolysaccharide
-
-
?
protein + H2O
peptides
tail specific pathway for removing abnormal cytoplasmic proteins via the enzyme, disposition by degradation of polypeptides synthesized from truncated mRNA molecules and are C-terminally tagged with an 11-amino-acid nonpolar destabilizing tail via a mechanism involving the 10Sa stable RNA
-
?
lambda Xis + H2O
?
-
protein substrate is required for site-specific excision of phage lambda from the bacterial chromosome
-
?
LpxC + H2O
?
-
ATP-dependent. Essentiality of FtsH lies in its function to keep the proper LPS/phospholipid ratio by degrading LpxC
-
-
?
phage lambda CII protein + H2O
small peptides
-
enzyme participates in the phage lambda lysis-lysogeny decision by degrading the CII transcriptional activator and by its response to inhibition by the lambda CIII gene product
-
?
protein F0 subunit a + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
protein LpxC + H2O
?
-
essential for cell viability, enzyme controls the steady-state level of the LpxC protein, which has a key regulatory role in the biosynthesis of lipopolysaccharides
-
?
protein YccA + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
sigma32 + H2O
?
-
hydrolyzes about 140 ATP molecules during the degradation of a single molecule of cy2-sigma32. Degradation of sigma32 proceeds from the N-terminus to the C-terminus
-
-
?
Protein + H2O
?
-
FtsH degrades misassembled membrane proteins and a subset of cytoplasmic regulatory proteins
-
-
?
Protein + H2O
?
-
the enzyme can unfold proteins with lower Tms such as glutathione S-transferase (Tm: 52°C)
-
-
?
protein + H2O
peptides
-
degradation of regulatory proteins to control gene activity and metabolism
-
?
protein + H2O
peptides
-
degrades misassembled membrane protein complexes and plays a vital role in membrane quality control, degrades cytoplasmic regulatory proteins
-
?
protein + H2O
peptides
-
enzyme affects several processes including cell division, the synthesis of phospholipids and lipopolysaccharides, the anchoring of integral membrane proteins, mRNA stability, and colchicin tolerance, degradation of membrane proteins, essentially required as a membrane-integrated quality control
-
?
protein + H2O
peptides
-
housekeeping function, because the enzyme lacks a robust unfoldase activity, it is able to use the substrate protein folding state as a criterion for degradation
-
?
protein + H2O
peptides
-
involved in membrane protein assembly as well as degradation of unstable proteins
-
?
protein + H2O
peptides
-
involved in the degradation of regulatory proteins and uncomplexed subunits of membrane protein complexes
-
?
protein + H2O
peptides
-
FtsH degrades a set of short-lived proteins, enabling cellular regulation at the level of protein stability. FtsH also degrades some misassembles membrane proteins, contributing to their quality maintenance. One biological role of FtsH might be to affect the development and life cycle of infecting or episomal genetic systems, by degrading their key regulatory molecules. The enzyme has a special ability to dislocate membrane protein substrates out of the membrane for which its own membrane-embedded nature is essential
-
-
?
protein SecY + H2O
?
-
uncomplexed subunit of the protein translocase
-
?
protein SecY + H2O
?
-
degradation of membrane protein, essentially required as a membrane-integrated quality control
-
?
protein SecY + H2O
?
-
quality control, the enzyme regulates the amount of SecY assembled in the mitochondrial membrane, elimination of uncomplexed SecY is important for optimum protein translocation and for the integrity of the membrane
-
?
protein SecY + H2O
?
-
SecY protein is a subunit of protein translocase
-
?
additional information
?
-
FtsH functions as a membrane chaperone and protease. FtsH and YidC have a linked role in the quality control of inner membrane proteins
-
-
?
additional information
?
-
-
dislocation of membrane proteins mediated by the enzyme, periplasmic segments can also be degraded by the enzyme
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATPgammaS
-
wild-type enzyme and mutants, dependent on protein substrate, low activity
ATP
certain acidic residues in both the pore-1 and pore-2 loops are important for ATPase activity
ATP
-
dependent on
649174, 651232, 651279, 651634, 651654, 651691, 651704, 652391, 652491, 652822, 653608, 653690, 668731, 719955
ATP
-
ATP binding is not necessary for enzyme assembly, enzyme contains conserved Walker-type ATPase domain of approximately 230 amino acids, dependent on, hydrolysis induces conformational changes
ATP
-
dependent on, 2 ATP binding consensus sequences, 1 is located at the C-terminus and is essential for proteolytic activity
ATP
-
dependent on, enzyme is the only essential ATP-dependent protease in Escherichia coli
ATP
-
dependent on, induces conformational changes by binding irrespective of ATP hydrolysis
ATP
-
dependent on, large cytoplasmic domain contains ATPase and protease activities
ATP
-
dependent on, the Walker-type ATPase modul is an alpha/beta-nucleotide binding domain connected to a four-helix bundle
additional information
-
no activity with adenosine5'-(beta,gamma-imino)triphosphate
-
additional information
-
no activity with ADP, wild-type enzyme and mutants
-
additional information
-
no activity with ATPgammaS, absolutely dependent on nucleoside 5'-triphosphates like ATP or CTP, not GTP or UTP, or derivatives
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
additional information
Zn2+
-
zinc metalloprotease, essential zinc binding sequence motif HEXXH at the cytoplasmic domain
additional information
-
conserved metal-binding motif HEXGH at the proteolytic centre
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Dimethylsulfoxide
-
induces conformational changes, stimulates with SecY as substrate, at concentration up to 20% v/v, slightly inhibitory with casein as a substrate
phage lambda CIII protein
-
enzyme participates in the phage lambda lysis-lysogeny decision by degrading the CII transcriptional activator and by its response to inhibition by the lambda CIII gene product
-
protein SecE
-
stabilizes overexpressed SecY against proteolytic degradation by the enzyme, acts a an antagonist
-
additional information
-
neither GTP nor GDP inhibit proteolytic activity of FtsH per se, but GTP/GDP binding stabilizes bacterial cell division protein FtsZ against degradation by FtsH
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
ATP-dependent metalloendoprotease belonging to the AAA family (ATPases associated with diverse cellular activities)
dimethylsulfoxid
-
induces conformational changes, stimulates with SecY s substrate, at concentration up to 20% v/v, slightly inhibitory with casein as a substrate
succinate
-
stimulates, antagonist of carbonyl cyanide-3-chlorophenylhydrazone
additional information
-
stimulation by the proton motive force through the transmembrane region
-
additional information
-
unfolded or uncomplexed protein substrates, protein sigma32 and casein, stimulate 1 to 2fold the wild-type enzyme and the mutants F228K, F228E, and F228A, but not G230A
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.122
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.1
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
enzyme contains 2 transmembrane segments at the N-terminus and a large cytoplasmic domain
-
-
integral, schematic model of structure and arrangement in the membane
-
-
the N-terminus mediates membrane association as well as homooligomeric interaction
-
-
FtsH has N-terminally located transmembrane segments and a main cytosolic region consisting of AAA-ATPase and Zn2+-metalloprotease domains
-
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
dependence of degradation rates on ATP hydrolysis rates is highly nonlinear. At least, about 20 ATP hydrolysis events need to be accumulated per minute for degradation to occur, but once exceeding the threshold, FtsH tightly couples ATP hydrolysis to degradation in a highly cooperative manner (Hill coefficinet for ATP is 4-5). The degradation rates steeply increase and saturate at the ATP hydrolysis rates far below the maxima. During the steep increase, FtsH efficiently utilizes ATP hydrolysis for degradation, consuming only 40-60% of the total ATP cost measured at the maximal ATP hydrolysis rates
malfunction
-
expression of doxorubicin resistance protein B alone or doxorubicin resistance protein AB together in FtsH-deficient cells results in growth inhibition
metabolism
-
the enzyme facilitates refolding of previously misassembled membrane protein doxorubicin resistance protein AB
physiological function
physiological function
-
FtsH controls lipopolysaccharide biosynthesis by proteolysis of LpxC
physiological function
-
FtsH is necessary for the processing of colicinsD and E3 during their import into the cytoplasm
physiological function
-
uncomplexed phage shock protein C is deleterious to the bacterial cell and FtsH acts as an important quality control mechanism to remove it
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the large complexes exhibit either ATPase and protease activity, while smaller ones do not
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
homohexamer
additional information
homohexamer
-
the FtsH holoenzyme is a ring-shaped homohexamer forming a complex of up to 1 MDa together with the membrane proteins QmcA and HflKC
additional information
-
C-terminal region of the enzyme, residues 541-585, forms a coiled-coil, leucine-zipper structure, three of the leucine residues are essential
additional information
-
enzyme consists of a membrane-anchoring region of amino acids 1-123 in the N-terminus, and a cytoplasmic region of amino acids 124-647 in the C-terminus, enzyme forms homooligomers
additional information
-
enzyme is composed of an N-terminal membrane-spanning region and a large cytoplasmic domain which contains ATPase and protease activities
additional information
-
enzyme shows a ring-shaped structure, ATP binding is not necessary for enzyme assembly
additional information
-
highly conserved residues Phe228 and Gly230 lie in the central pore region of the hexamer
additional information
-
molecular structure model of the AAA domain, intersubunit interactions, overview
additional information
-
the N-terminus mediates membrane association as well as homooligomeric interaction
additional information
-
FtsH exists exclusively as a characteristic large complex, termed FtsH holo-enzyme of greater than 30S, with HflK and HflC
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
ATP-dependent C-terminally self-processing by cleavage of Met640-Ser641 bond removing a heptapeptide from the C-terminus, preference for positively charged and hydrophobic amino acid residues, both processed and unprocessed enzyme forms are active, levels depending on the growth phase
proteolytic modification
-
autocatalytically processed at the C-terminus, processing occurs preferentially after positively charged and hydrophobic amino acids
proteolytic modification
-
FtsH undergoes self-cleavage between M640 and S641, removing seven C-terminal residues. Functional significance of this self-cleavage reaction is obscure, as both the full-length and the processed forms of FtsH are active as protease
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapour-diffusion method, AAA domain solution: 10 mg/ml protein, 20 mM Tris-HCl, pH 8.5, 50 mM NaCl, 1 mM DTT, precipitant is 1.5 M ammonium sulfate, 2 to 3 days, X-ray structure determination and analysis at about 1.5 A
-
X-ray structure determination and analysis at about 1.5 A, molecular modeling
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C229F
ATPase activity is 114% of wild-type activity, protease activity with BODIPY-casein is 47% of wild-type activity, protease activity with Cy3-sigma32 is 22% of wild-type activity
D223K
ATPase activity is 20% of wild-type activity, protease activity with BODIPY-casein is 10% of wild-type activity, protease activity with Cy3-sigma32 is 5% of wild-type activity
D272N
ATPase activity is 97% of wild-type activity, protease activity with BODIPY-casein is 81% of wild-type activity
E226A
ATPase activity is 10% of wild-type activity, protease activity with BODIPY-casein is 11% of wild-type activity
E226K
ATPase activity is less than 5% of wild-type activity, protease activity with BODIPY-casein is 6% of wild-type activity
E226Q
ATPase activity is 20% of wild-type activity, protease activity with BODIPY-casein is 18% of wild-type activity, protease activity with Cy3-sigma32 is 17% of wild-type activity
E273A
ATPase activity is 20% of wild-type activity, protease activity with BODIPY-casein is 8% of wild-type activity, protease activity with Cy3-sigma32 is less than 5% of wild-type activity
E273D
ATPase activity is 143% of wild-type activity, protease activity with BODIPY-casein is 82% of wild-type activity
E273K
ATPase activity is less 5% of wild-type activity, protease activity with BODIPY-casein is 7% of wild-type activity
E273Q
ATPase activity is 68% of wild-type activity, protease activity with BODIPY-casein is 50% of wild-type activity, protease activity with Cy3-sigma32 is 11% of wild-type activity
H271D
ATPase activity is 78% of wild-type activity, protease activity with BODIPY-casein is 39% of wild-type activity, protease activity with Cy3-sigma32 is 20% of wild-type activity
M227K
ATPase activity is 55% of wild-type activity, protease activity with BODIPY-casein is 69% of wild-type activity, protease activity with Cy3-sigma32 is 8% of wild-type activity
E415K
-
site-directed mutagenesis, mutation of the zinc binding sequence motif, reduced proteolytic activity
F228A
-
site-directed point mutation, proteolytically inactive with protein sigma32, but degrades casein, decreased ATPase activity
F228E
-
site-directed point mutation, proteolytically inactive mutant, increased ATPase activity
F228K
-
site-directed point mutation, proteolytically inactive mutant, highly decreased ATPase activity
G230A
-
site-directed point mutation, proteolytically inactive mutant, highly decreased ATPase activity
H417A/E418Q/H421A
-
the mutant shows 106% ATPase activity compared to the wild type enzyme
K136N
-
site-directed mutagenesis, mutation is located in a second ATP binding site, activity is slightly reduced, can complement a deficient mutant strain
K198N
L189W
-
mutation ftsH102, partial complementation of temperature sensitivity of the ftsH1 mutant at 42°C but not other cols-sensitive mutants, overview
L567R
-
site-directed mutagenesis, mutation in the C-terminal coiled-coil structure, mutant is defective in binding and degradation of sigma32 protein and phage lambda CII protein, no growth of phage lambda
L574A
-
site-directed mutagenesis, mutation in the C-terminal coiled-coil structure, mutant is defective in binding and degradation of sigma32 protein and phage lambda CII protein, no growth of phage lambda
L574R
-
site-directed mutagenesis, mutation in the C-terminal coiled-coil structure, mutant is defective in binding and degradation of sigma32 protein and phage lambda CII protein, no growth of phage lambda
L581R
-
site-directed mutagenesis, mutation in the C-terminal coiled-coil structure, mutant is defective in binding and degradation of sigma32 protein and phage lambda CII protein, no growth of phage lambda
S137N
-
site-directed mutagenesis, mutation is located in a second ATP binding site, activity is slightly reduced, can complement a deficient mutant strain
T199A
-
site-directed mutagenesis, mutation is located in the C-terminal ATP binding site, inactive, no complementation of a deficient mutant strain
T199N
-
site-directed mutagenesis, mutation is located in the C-terminal ATP binding site, highly reduced activity, weak complementation of a deficient mutant strain
additional information
K198N
-
site-directed mutagenesis, mutation is located in the C-terminal ATP binding site, inactive, no complementation of a deficient mutant strain
K198N
-
the mutant shows 12% ATPase activity compared to the wild type enzyme
additional information
enzyme mutant still shows activity with substrates derivative of the N-terminal domain of the lambdacI repressor tagged with cI105 and SsrA
additional information
-
construction of mutants by deletion of N-terminal membrane region, replacement by a leucine-zipper, or replacement by a lactose permease transmembrane segment, the matated proteins show very low remaining activity, but are stimulated by dimethylsulfoxide, the deletion mutant does not show ATPase and proteolytic activity
additional information
-
defects in the ftsH gene stabilize the SecY protein, overexpression increase the degradation of SecY, enzyme deficient mutantion ftsH101 suppresses the temperature-sensitive export defect of a secY24 mutant G240D in the cytoplasmic domain of SecY by stabilizing the mutant protein
additional information
-
enzyme mutation stabilizes the cII and cIII proteins resulting in greater levels of the cI repressor and thus shifting the lytic-lysogeny decision in favor of the lysogeny, lon ftsH double mutant shows 6fold reduced activity with lambda Xis protein, which accumulates and interferes with the integration of lambda
additional information
-
mutational amino acid exchange of the self-processing site M640-S641 reveal the preference for positively charged and hydrophobic amino acid residues at this site for proteolytic cleavage
additional information
-
mutations cause an abnormal orientation of some model proteins in the plasma membrane, the effect can be supressed by overexpression of molecular-chaperone proteins, deletion of FtsH is lethal
additional information
-
several mutant strains harboring mutations in the C-terminal coiled-coil leucine-zipper structure, are defective in binding and degradation of sigma32 protein and the phage lambda CII proteins, the mutations do not interfere with the ATPase activity, the mutants are more sensitive against trypsin digestion than the wild-type and show reduced growth
additional information
-
soluble form of the enzyme having only the cytoplasmic C-terminal region is inactive, construction of maltose-binding protein fusion proteins with fusion at 5 different N-termini of the enzyme, i.e. MF1-5, shorter constructs lacking the second transmembrane segment are proteolytically inactive and do not form oligomers, while the longer constructs are similar to the wild-type
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme, solubilization by N-lauylsarcosine, refolding in presence of ATP, Mg2+ and Zn2+, and purification to near homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of AAA domain residues 126-398 as tagged protein in strain AR5088
-
expression of GST-wild-type enzyme fusion protein, expression of coiled-coil structure mutant enzymes, expression of coiled-coil C-terminus, residues 541-585, as His-tagged peptide
-
expression of His-Myc-tagged wild-type and mutant enzymes from strain TY024
-
expression of wild-type enzyme in Escherichia coli strain AD465 as His-tagged and Myc-tagged protein
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
construction of an in vitro reaction system in which the enzyme is membrane embedded and not solubilized by detergent, two inverted membrane vesicles or proteoliposomes, one bearing the enzyme, the other bearing the substrate protein, are fused, reconstituted enzyme is accessible to proteinase K because the ATPase and protease are exposed outside the vesicles
-
recombinant enzyme, solubilization by N-lauylsarcosine, refolding in presence of ATP, Mg2+ and Zn2+, and purification to near homogeneity, the refolded enzyme has properties similar to the overexpressed solubilized one
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Krzywda, S.; Brzozowski, A.M.; Karata, K.; Ogura, T.; Wilkinson, A.J.
Crystallization of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli
Acta Crystallogr. Sect. D
58
1066-1067
2002
Escherichia coli
Langer, T.; Kaser, M.; Klanner, C.; Leonhard, K.
AAA proteases of mitochondria: quality control of membrane proteins and regulatory functions during mitochondrial biogenesis
Biochem. Soc. Trans.
29
431-436
2001
Escherichia coli
Akiyama, Y.
Self-processing of FtsH and its implication for the cleavage specificity of this protease
Biochemistry
38
11693-11699
1999
Escherichia coli
Akiyama, Y.; Ito, K.
Roles of homooligomerization and membrane association in ATPase and proteolytic activities of FtsH in vitro
Biochemistry
40
7687-7693
2001
Escherichia coli
Bruckner, R.C.; Gunyuzlu, P.L.; Stein, R.L.
Coupled kinetics of ATP and peptide hydrolysis by Escherichia coli FtsH protease
Biochemistry
42
10843-10852
2003
Escherichia coli
Akiyama, Y.; Kihara, A.; Ito, K.
Subunit a of proton ATPase F0 sector is a substrate of the FtsH protease in Escherichia coli
FEBS Lett.
399
26-28
1996
Escherichia coli
Makino, S.; Makino, T.; Abe, K.; Hashimoto, J.; Tatsuta, T.; Kitagawa, M.; Mori, H.; Ogura, T.; Fujii, T.; Fushinobu, S.; Wakagi, T.; Matsuzawa, H.; Makinoa, T.
Second transmembrane segment of FtsH plays a role in its proteolytic activity and homo-oligomerization
FEBS Lett.
460
554-558
1999
Escherichia coli
Bertani, D.; Oppenheim, A.B.; Narberhaus, F.
An internal region of the RpoH heat shock transcription factor is critical for rapid degradation by the FtsH protease
FEBS Lett.
493
17-20
2001
Escherichia coli
Herman, C.; Thevenet, D.; Bouloc, P.; Walker, G.C.; D'Ari, R.
Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH)
Genes Dev.
12
1348-1355
1998
Escherichia coli (P0AAI3)
Leffers, G.G., Jr.; Gottesman, S.
Lambda Xis degradation in vivo by Lon and FtsH
J. Bacteriol.
180
1573-1577
1998
Escherichia coli
Shotland, Y.; Shifrin, A.; Ziv, T.; Teff, D.; Koby, S.; Kobiler, O.; Oppenheim, A.B.
Proteolysis of bacteriophage lambda CII by Escherichia coli FtsH (HflB)
J. Bacteriol.
182
3111-3116
2000
Escherichia coli
Tomoyasu, T.; Arsene, F.; Ogura, T.; Bukau, B.
The C terminus of sigma(32) is not essential for degradation by FtsH
J. Bacteriol.
183
5911-5917
2001
Escherichia coli
Chiba, S.; Akiyama, Y.; Ito, K.
Membrane protein degradation by FtsH can be initiated from either end
J. Bacteriol.
184
4775-4782
2002
Escherichia coli
Akiyama, Y.; Kihara, A.; Tokuda, H.; Ito, K.
FtsH (HflB) is an ATP-dependent protease selectively acting on SecY and some other membrane proteins
J. Biol. Chem.
271
31196-31201
1996
Escherichia coli
Akiyama, Y.; Ito, K.
Reconstitution of membrane proteolysis by FtsH
J. Biol. Chem.
278
18146-18153
2003
Escherichia coli
Yamada-Inagawa, T.; Okuno, T.; Karata, K.; Yamanaka, K.; Ogura, T.
Conserved pore residues in the AAA protease, FtsH, are important for proteolysis and its coupling to ATP hydrolysis
J. Biol. Chem.
278
50182-50187
2003
Escherichia coli
Shotland, Y.; Teff, D.; Koby, S.; Kobiler, O.; Oppenheim, A.B.
Characterization of a conserved alpha-helical, coiled-coil motif at the C-terminal domain of the ATP-dependent FtsH (HflB) protease of Escherichia coli
J. Mol. Biol.
299
953-964
2000
Escherichia coli
Herman, C.; Prakash, S.; Lu, C.Z.; Matouschek, A.; Gross, C.A.
Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH
Mol. Cell
11
659-669
2003
Escherichia coli
Kihara, A.; Akiyama, Y.; Ito, K.
FtsH is required for proteolytic elimination of uncomplexed forms of SecY, an essential protein translocase subunit
Proc. Natl. Acad. Sci. USA
92
4532-4536
1995
Escherichia coli
Akiyama, Y.
Proton-motive force stimulates the proteolytic activity of FtsH, a membrane-bound ATP-dependent protease in Escherichia coli
Proc. Natl. Acad. Sci. USA
99
8066-8071
2002
Escherichia coli
Krzywda, S.; Brzozowski, A.M.; Verma, C.; Karata, K.; Ogura, T.; Wilkinson, A.J.
The crystal structure of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli at 1.5 A resolution
Structure
10
1073-1083
2002
Escherichia coli
Ito, K.; Akiyama, Y.
Cellular functions, mechanism of action, and regulation of FtsH protease
Annu. Rev. Microbiol.
59
211-231
2005
Escherichia coli
Adam, Z.; Rudella, A.; van Wijk, K.J.
Recent advances in the study of Clp, FtsH and other proteases located in chloroplasts
Curr. Opin. Plant Biol.
9
234-240
2006
Escherichia coli
Okuno, T.; Yamanaka, K.; Ogura, T.
An AAA protease FtsH can initiate proteolysis from internal sites of a model substrate, apo-flavodoxin
Genes Cells
11
261-268
2006
Escherichia coli
Saikawa, N.; Akiyama, Y.; Ito, K.
FtsH exists as an exceptionally large complex containing HflKC in the plasma membrane of Escherichia coli
J. Struct. Biol.
146
123-129
2004
Escherichia coli
Okuno, T.; Yamada-Inagawa, T.; Karata, K.; Yamanaka, K.; Ogura, T.
Spectrometric analysis of degradation of a physiological substrate sigma32 by Escherichia coli AAA protease FtsH
J. Struct. Biol.
146
148-154
2004
Escherichia coli
Okuno, T.; Yamanaka, K.; Ogura, T.
Characterization of mutants of the Escherichia coli AAA protease, FtsH, carrying a mutation in the central pore region
J. Struct. Biol.
156
109-114
2006
Escherichia coli (P0AAI3)
Srinivasan, R.; Rajeswari, H.; Bhatt, B.N.; Indi, S.; Ajitkumar, P.
GTP/GDP binding stabilizes bacterial cell division protein FtsZ against degradation by FtsH protease in vitro
Biochem. Biophys. Res. Commun.
357
38-43
2007
Escherichia coli
Licht, S.; Lee, I.
Resolving individual steps in the operation of ATP-dependent proteolytic molecular machines: from conformational changes to substrate translocation and processivity
Biochemistry
47
3595-3605
2008
Escherichia coli
Srinivasan, R.; Ajitkumar, P.
Bacterial cell division protein FtsZ is stable against degradation by AAA family protease FtsH in Escherichia coli cells
J. Basic Microbiol.
47
251-259
2007
Escherichia coli
Fuehrer, F.; Mueller, A.; Baumann, H.; Langklotz, S.; Kutscher, B.; Narberhaus, F.
Sequence and length recognition of the C-terminal turnover element of LpxC, a soluble substrate of the membrane-bound FtsH protease
J. Mol. Biol.
372
485-496
2007
Escherichia coli, Escherichia coli W3110 / ATCC 27325
Okuno, T.; Yamanaka, K.; Ogura, T.
Flavodoxin, a new fluorescent substrate for monitoring proteolytic activity of FtsH lacking a robust unfolding activity
J. Struct. Biol.
156
115-119
2006
Escherichia coli, Escherichia coli AR5771
Srinivasan, R.; Rajeswari, H.; Ajitkumar, P.
Analysis of degradation of bacterial cell division protein FtsZ by the ATP-dependent zinc-metalloprotease FtsH in vitro
Microbiol. Res.
163
21-30
2008
Escherichia coli, Escherichia coli TYE024
Obrist, M.; Milek, S.; Klauck, E.; Hengge, R.; Narberhaus, F.
Region 2.1 of the Escherichia coli heat-shock sigma factor RpoH (sigma32) is necessary but not sufficient for degradation by the FtsH protease
Microbiology
153
2560-2571
2007
Escherichia coli
Fuehrer, F.; Langklotz, S.; Narberhaus, F.
The C-terminal end of LpxC is required for degradation by the FtsH protease
Mol. Microbiol.
59
1025-1036
2006
Escherichia coli, Escherichia coli W3110 / ATCC 27325
van Bloois, E.; Dekker, H.L.; Froederberg, L.; Houben, E.N.; Urbanus, M.L.; de Koster, C.G.; de Gier, J.W.; Luirink, J.
Detection of cross-links between FtsH, YidC, HflK/C suggests a linked role for these proteins in quality control upon insertion of bacterial inner membrane proteins
FEBS Lett.
582
1419-1424
2008
Escherichia coli (P0AAI3)
Obrist, M.; Langklotz, S.; Milek, S.; Fuehrer, F.; Narberhaus, F.
Region C of the Escherichia coli heat shock sigma factor RpoH (sigma 32) contains a turnover element for proteolysis by the FtsH protease
FEMS Microbiol. Lett.
290
199-208
2009
Escherichia coli (P0AAI3)
Katz, C.; Ron, E.Z.
Dual role of FtsH in regulating lipopolysaccharide biosynthesis in Escherichia coli
J. Bacteriol.
190
7117-7122
2008
Escherichia coli (P0AAI3)
Langklotz, S.; Schaekermann, M.; Narberhaus, F.
Control of lipopolysaccharide biosynthesis by FtsH-mediated proteolysis of LpxC is conserved in enterobacteria but not in all gram-negative bacteria
J. Bacteriol.
193
1090-1097
2011
Escherichia coli, Escherichia coli W3110 / ATCC 27325
Singh, S.; Darwin, A.J.
FtsH-dependent degradation of phage shock protein C in Yersinia enterocolitica and Escherichia coli
J. Bacteriol.
193
6436-6442
2011
Escherichia coli, Yersinia enterocolitica, Yersinia enterocolitica AJD3
Chauleau, M.; Mora, L.; Serba, J.; de Zamaroczy, M.
FtsH-dependent processing of RNase colicins D and E3 means that only the cytotoxic domains are imported into the cytoplasm
J. Biol. Chem.
286
29397-29407
2011
Escherichia coli, Escherichia coli C600
Schaekermann, M.; Langklotz, S.; Narberhaus, F.
FtsH-mediated coordination of lipopolysaccharide biosynthesis in Escherichia coli correlates with the growth rate and the alarmone (p)ppGpp
J. Bacteriol.
195
1912-1919
2013
Escherichia coli, Escherichia coli W3110 / ATCC 27325
Li, W.; Rao, D.K.; Kaur, P.
Dual role of the metalloprotease FtsH in biogenesis of the DrrAB drug transporter
J. Biol. Chem.
288
11854-11864
2013
Escherichia coli, Escherichia coli AR796
Bittner, L.M.; Westphal, K.; Narberhaus, F.
Conditional proteolysis of the membrane protein YfgM by FtsH depends on a novel N-terminal degron
J. Biol. Chem.
290
19367-19378
2015
Escherichia coli, Escherichia coli W3110 / ATCC 27325
Hari, S.B.; Sauer, R.T.
The AAA+ FtsH protease degrades an ssrA-tagged model protein in the inner membrane of Escherichia coli
Biochemistry
55
5649-5652
2016
Escherichia coli (C3SSK2)
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