Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.6.4.7 extracted from

  • Grimm, I.; Erdmann, R.; Girzalsky, W.
    Role of AAA+-proteins in peroxisome biogenesis and function (2016), Biochim. Biophys. Acta, 1863, 828-837.
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
analysis of the crystal structures of the extreme N-terminal part of murine Pex1p exposed a double-psi-beta-barrel fold with similarities to adaptor binding domains of p97 and NSF Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Escherichia coli 5829
-
cytosol the Pex1p/Pex6p-complex shows a dual localization in the cell as it is located in the cytosol as well as at the peroxisomal membrane Saccharomyces cerevisiae 5829
-
additional information four Lon isoforms localize to mitochondria, plastids and peroxisomes.The peroxisome specific enzyme is Lon2, which carries a PTS1-signal Arabidopsis thaliana
-
-
additional information presence of two Lon isoforms with one of them located in the peroxisomal matrix Ogataea angusta
-
-
additional information the AAAdomains of Pex6p seem to influence the Pex6p/Pex15p-interaction and thereby regulate the recruitment of the cytosolic AAA-complex to the peroxisomal membrane, although in opposite fashion. In particular, ATP-binding to D1 of Pex6p stimulates association of the AAA-complex with Pex15p at the peroxisomal membrane while ATP-hydrolysis at D2 seems to trigger the release of the AAA-complex from Pex15p and thus from the membrane Saccharomyces cerevisiae
-
-
additional information the tail-anchored protein Pex15p in yeast functions as membrane anchors responsible for the recruitment of the Pex1p-Pex6p complex to the peroxisomal membrane, the N-terminal domain of Pex6p interacts with the cytosolic part of Pex15p and mediates the attachment of the Pex1p-Pex6p complex to the membrane Saccharomyces cerevisiae
-
-
additional information the tail-anchored protein Pex26p in humans functions as membrane anchors responsible for the recruitment of the Pex1p-Pex6p complex to the peroxisomal membrane, the N-terminal domain of Pex6p interacts with the cytosolic part of Pex26p and mediates the attachment of the Pex1p-Pex6p complex to the membrane Homo sapiens
-
-
additional information the tail-anchored protein Pex26p in humans functions as membrane anchors responsible for the recruitment of the Pex1p-Pex6p complex to the peroxisomal membrane, the N-terminal domain of Pex6p interacts with the cytosolic part of Pex26p and mediates the attachment of the Pex1p–Pex6p complex to the membrane Homo sapiens
-
-
peroxisomal membrane the Pex1p/Pex6p-complex shows a dual localization in the cell as it is located in the cytosol as well as at the peroxisomal membrane. Association of this complex with the peroxisomal membrane is mediated by binding to Pex15p. The predominant part of the tail anchored protein Pex15p faces the cytosol and mediates the peroxisomal membrane association of the AAA-complex via a direct interaction with the N-terminal domain of Pex6p, assembly of the Pex1p/Pex6p-complex and recruitment to the peroxisomal membrane Saccharomyces cerevisiae 5778
-
peroxisomal membrane the Pex1p/Pex6p-complex shows a dual localization in the cell as it is located in the cytosol as well as at the peroxisomal membrane. Association of this complex with the peroxisomal membrane is mediated by binding to Pex15p. The predominant part of the tail-anchored protein Pex15p faces the cytosol and mediates the peroxisomal membrane association of the AAA-complex via a direct interaction with the N-terminal domain of Pex6p, assembly of the Pex1p/Pex6p-complex and recruitment to the peroxisomal membrane Saccharomyces cerevisiae 5778
-
peroxisome Pex1p is targeted to peroxisomes in a manner dependent on ATP hydrolysis, while Pex6p targeting requires ATP but not its hydrolysis Saccharomyces cerevisiae 5777
-
peroxisome structural organization and localization of peroxisomal AAA+ ATPases Penicillium chrysogenum 5777
-
peroxisome structural organization and localization of peroxisomal AAA+ ATPases, peroxisomal matrix isozyme Ogataea angusta 5777
-
peroxisome structural organization and localization of peroxisomal AAA+ ATPases. Dynamic Pex1p-Pex6p complex assembly at the peroxisomal membrane Homo sapiens 5777
-
peroxisome structural organization and localization of peroxisomal AAA+ ATPases. Dynamic Pex1p-Pex6p complex assembly at the peroxisomal membrane Saccharomyces cerevisiae 5777
-
peroxisome structural organization and localization of peroxisomal AAA+ ATPases. Dynamic Pex1p-Pex6p complex assembly at the peroxisomal membrane Mus musculus 5777
-
peroxisome structural organization and localization of peroxisomal AAA+ ATPases. The peroxisome specific isozyme is Lon2, which carries a PTS1-signal Arabidopsis thaliana 5777
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Arabidopsis thaliana
Mg2+ required Escherichia coli
Mg2+ required Homo sapiens
Mg2+ required Saccharomyces cerevisiae
Mg2+ required Ogataea angusta
Mg2+ required Penicillium chrysogenum
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O Arabidopsis thaliana
-
ADP + phosphate
-
?
ATP + H2O Escherichia coli
-
ADP + phosphate
-
?
ATP + H2O Homo sapiens
-
ADP + phosphate
-
?
ATP + H2O Saccharomyces cerevisiae
-
ADP + phosphate
-
?
ATP + H2O Ogataea angusta
-
ADP + phosphate
-
?
ATP + H2O Penicillium chrysogenum
-
ADP + phosphate
-
?
ATP + H2O Mus musculus
-
ADP + phosphate
-
?
additional information Saccharomyces cerevisiae model of Pex5p export by threading through the central Pex1p-Pex6p pore, overview ?
-
?

Organism

Organism UniProt Comment Textmining
Arabidopsis thaliana O64948 Lon2
-
Escherichia coli P0A9M0
-
-
Homo sapiens O43933 PEX1; gene PEX1
-
Homo sapiens Q13608 PEX6; gene PEX6
-
Mus musculus Q5BL07 PEX1
-
Mus musculus Q99LC9 PEX6
-
Ogataea angusta Q2V573
-
-
Penicillium chrysogenum B6HJQ3
-
-
Saccharomyces cerevisiae P24004 gene PEX1
-
Saccharomyces cerevisiae P24004 PEX1
-
Saccharomyces cerevisiae P33760 gene PEX6
-
Saccharomyces cerevisiae P33760 PEX6
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O
-
Arabidopsis thaliana ADP + phosphate
-
?
ATP + H2O
-
Escherichia coli ADP + phosphate
-
?
ATP + H2O
-
Homo sapiens ADP + phosphate
-
?
ATP + H2O
-
Saccharomyces cerevisiae ADP + phosphate
-
?
ATP + H2O
-
Ogataea angusta ADP + phosphate
-
?
ATP + H2O
-
Penicillium chrysogenum ADP + phosphate
-
?
ATP + H2O
-
Mus musculus ADP + phosphate
-
?
additional information model of Pex5p export by threading through the central Pex1p-Pex6p pore, overview Saccharomyces cerevisiae ?
-
?

Subunits

Subunits Comment Organism
heterohexamer AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, Pex1p/Pex6p forms a type II heterohexameric complex with two AAA+ rings (D1 ring, D2 ring) and large N-terminal domains positioned on top and aside of the double ring structure Homo sapiens
heterohexamer AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, Pex1p/Pex6p forms a type II heterohexameric complex with two AAA+ rings (D1 ring, D2 ring) and large N-terminal domains positioned on top and aside of the double ring structure Saccharomyces cerevisiae
heterohexamer AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, Pex1p/Pex6p forms a type II heterohexameric complex with two AAA+ rings (D1 ring, D2 ring) and large N-terminal domains positioned on top and aside of the double ring structure Mus musculus
homohexamer AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment Arabidopsis thaliana
homohexamer AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment Escherichia coli
homohexamer AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment Ogataea angusta
homohexamer AAA+ modules consist of an ASCE domain and a C-terminal attached C-domain. The ASCE domain harbors the Walker A (p-loop) and Walker B motifs as well as the Sensor 1 and arginine-fingers (Arg-finger) within the second region of homology (SRH). The Sensor 2 is located in the C-domain. Hexameric ring formation with ATP binding sides located between the interfaces of the AAA+ protomers, the enzyme combines its AAA+ ring with a C-terminal protease segment Penicillium chrysogenum
More since interaction of Pex1p and Pex6p strongly depends on accurate nucleotide binding, heterohexameric complex formation might be a reversible process, autoregulated by the ATPase cycle of the AAA+-peroxins Mus musculus
More since interaction of Pex1p and Pex6p strongly depends on accurate nucleotide binding, heterohexameric complex formation might be a reversible process, autoregulated by the ATPase cycle of the AAA+-peroxins. Under ATP depletion, Pex6p remains at the peroxisomal membrane, whereas Pex1p is released to the cytosol, probably as homotrimeric version Homo sapiens
More when the yeast Pex1p-Pex6p complex disassembles under ATP depleting conditions, Pex1p adopts a homotrimeric conformation, while Pex6p is monomeric. Since interaction of Pex1p and Pex6p strongly depends on accurate nucleotide binding, heterohexameric complex formation might be a reversible process, autoregulated by the ATPase cycle of the AAA+-peroxins Saccharomyces cerevisiae

Synonyms

Synonyms Comment Organism
APEM10
-
Arabidopsis thaliana
lon
-
Arabidopsis thaliana
lon
-
Escherichia coli
lon
-
Ogataea angusta
lon
-
Penicillium chrysogenum
lon protease
-
Arabidopsis thaliana
lon protease
-
Escherichia coli
lon protease
-
Ogataea angusta
lon protease
-
Penicillium chrysogenum
lon2
-
Arabidopsis thaliana
peroxisomal Lon-protease
-
Arabidopsis thaliana
peroxisomal Lon-protease
-
Escherichia coli
peroxisomal Lon-protease
-
Ogataea angusta
peroxisomal Lon-protease
-
Penicillium chrysogenum
Pex1p
-
Homo sapiens
Pex1p
-
Saccharomyces cerevisiae
Pex1p
-
Mus musculus
Pex1p-Pex6p complex
-
Saccharomyces cerevisiae
Pex1p/Pex6p
-
Homo sapiens
Pex1p/Pex6p
-
Saccharomyces cerevisiae
Pex1p/Pex6p
-
Mus musculus
Pex6p
-
Homo sapiens
Pex6p
-
Saccharomyces cerevisiae
Pln
-
Penicillium chrysogenum

Expression

Organism Comment Expression
Saccharomyces cerevisiae binding of Pex15p to the Pex1p-Pex6p complex downregulates the ATPase activity of the AAA+-complex, possibly by influencing the D2 AAA+-domain of Pex1p down

General Information

General Information Comment Organism
evolution the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase Arabidopsis thaliana
evolution the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase Ogataea angusta
evolution the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase Penicillium chrysogenum
evolution the enzyme belongs to the a member of the Lon-family of proteases in the AAA+ ATPase superfamily, type I AAA+ ATPase. Based on the domain composition and sequence characteristic of the domains, the Lon-proteases are subdivided into two classes, LonA and LonB. The LonA subfamily are soluble enzymes,which function in the bacterial cytosol and the mitochondrial matrix, whereas LonB predominates in Archaea Escherichia coli
evolution the enzyme belongs to the AAA+ ATPase family. AAA-proteins belong to the class of P-loop NTPases defined by conserved motifs for NTP-binding (Walker A motif) and hydrolysis (Walker B motif) which are assisted by Mg2+ as cofactor. Pex1p and Pex6p are evolutionary related to Cdc48p/p97 Saccharomyces cerevisiae
evolution the enzyme belongs to the AAA+ ATPase superfamily Homo sapiens
evolution the enzyme belongs to the AAA+ ATPase superfamily Saccharomyces cerevisiae
evolution the enzyme belongs to the AAA+ ATPase superfamily Mus musculus
malfunction a deletion of peroxisomal Lon results in a specific growth defect on media containing oleic acid as a sole carbon source, conditions which require peroxisomal enzymes of the beta-oxidation pathway, the growth defect is accompanied by the formation of protein aggregates in the peroxisomal matrix Penicillium chrysogenum
malfunction a Lon protease deletion strain does not display a growth defect but a decreased viability of the cells Ogataea angusta
malfunction Lon2 absence leads to accumulation of enzymes in peroxisomes and results in an accelerated peroxisome degradation by pexophagy Arabidopsis thaliana
malfunction mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are themost common cause of the Zellweger spectrum diseases, the by far most abundant Pex1pG843D variation impairs the binding between Pex1p and Pex6p Homo sapiens
malfunction the PEX6-deletion strain has the most pronounced survival defects of all strains affected in peroxisome function Saccharomyces cerevisiae
metabolism the enzyme is involved in peroxisome biogenesis Arabidopsis thaliana
metabolism the enzyme is involved in peroxisome biogenesis Escherichia coli
metabolism the enzyme is involved in peroxisome biogenesis Homo sapiens
metabolism the enzyme is involved in peroxisome biogenesis Saccharomyces cerevisiae
metabolism the enzyme is involved in peroxisome biogenesis Ogataea angusta
metabolism the enzyme is involved in peroxisome biogenesis Penicillium chrysogenum
metabolism the enzyme is involved in peroxisome biogenesis Mus musculus
metabolism the enzyme is involved in peroxisome biogenesis, proteins that play a role in peroxisome biogenesis are collectively called peroxins. Function of Pex1p and Pex6p in peroxisomal matrix protein import, overview Saccharomyces cerevisiae
additional information structural organization and localization of peroxisomal AAA+ ATPases Arabidopsis thaliana
additional information structural organization and localization of peroxisomal AAA+ ATPases Escherichia coli
additional information structural organization and localization of peroxisomal AAA+ ATPases Ogataea angusta
additional information structural organization and localization of peroxisomal AAA+ ATPases Penicillium chrysogenum
additional information structural organization and localization of peroxisomal AAA+ ATPases, molecular organization of the Pex1p-Pex6p complex, modeling of the Pex1p-Pex6p mode of action, overview Homo sapiens
additional information structural organization and localization of peroxisomal AAA+ ATPases, molecular organization of the Pex1p-Pex6p complex, modeling of the Pex1p-Pex6p mode of action, overview Saccharomyces cerevisiae
additional information structure-function analysis. AAA-peroxins defective in ATP-hydrolysis of D1 are at least partially functional. In contrast, ATP-hydrolysis of the conserved AAA-domains (D2) of both AAA-peroxins is essential for their function. The conserved D2-domains of Pex1p and Pex6p require hydrolysis of ATP for their function in peroxisome biogenesis, indicating that they may provide the driving force for conformational changes triggered by the AAA-peroxins Saccharomyces cerevisiae
additional information structure-function analysis. The D1 of Pex6p does not contain a functional Walker B motif for ATP hydrolysis. AAA-peroxins defective in ATP-hydrolysis of D1 are at least partially functional. In contrast, ATP-hydrolysis of the conserved AAA-domains (D2) of both AAA-peroxins is essential for their function. The conserved D2-domains of Pex1p and Pex6p require hydrolysis of ATP for their function in peroxisome biogenesis, indicating that they may providethe driving force for conformational changes triggered by the AAA-peroxins Saccharomyces cerevisiae
additional information the murine Pex1p N-terminal domain lacks hydrophobic amino acids. Structural organization and localization of peroxisomal AAA+ ATPases, molecular organization of the Pex1p-Pex6p complex, modeling of the Pex1p-Pex6p mode of action, overview Mus musculus
physiological function Pex1p and Pex6p are crucial for peroxisome biogenesis, Pex6p functions together with Pex1p in peroxisome biogenesis. The ATP hydrolysis cycle of the AAA+-ATPases is supposed to regulate the assembly and disassembly of the Pex1p-Pex6p complex and its membrane association and release. Role of Pex1p in peroxisomal matrix protein import, overview Homo sapiens
physiological function Pex1p and Pex6p are crucial for peroxisome biogenesis, Pex6p functions together with Pex1p in peroxisome biogenesis. The ATP hydrolysis cycle of the AAA+-ATPases is supposed to regulate the assembly and disassembly of the Pex1p-Pex6p complex and its membrane association and release. Role of Pex1p/Pex6p in peroxisomal matrix protein import, overview Homo sapiens
physiological function Pex1p and Pex6p are crucial for peroxisome biogenesis, Pex6p functions together with Pex1p in peroxisome biogenesis. The ATP hydrolysis cycle of the AAA+-ATPases is supposed to regulate the assembly and disassembly of the Pex1p-Pex6p complex and its membrane association and release. Role of Pex6p in peroxisomal matrix protein import, overview Saccharomyces cerevisiae
physiological function Pex6p functions together with Pex1p in peroxisome biogenesis Mus musculus
physiological function the enzyme is essentially involved in peroxisome biogenesis, Pex1p provides the energy for import of peroxisomal matrix proteins. Peroxisomal matrix proteins are synthesized on free ribosomes in the cytosol and guided to the peroxisomal membrane by specific soluble receptors. At the membrane, the cargo-loaded receptors bind to a docking complex and the receptor-docking complex assembly is thought to form a dynamic pore which enables the transition of the cargo into the organellar lumen. The import cycle is completed by ubiquitination- and ATP-dependent dislocation of the receptor from the membrane to the cytosol, which is performed by the AAA-peroxins. Receptor ubiquitination and dislocation are the only energy-dependent steps in peroxisomal protein import. The export-driven import model suggests that the AAA-peroxins might function as motor proteins in peroxisomal import by coupling ATP-dependent removal of the peroxisomal import receptor and cargo translocation into the organelle Saccharomyces cerevisiae
physiological function the enzyme is essentially involved in peroxisome biogenesis, Pex6p provides the energy for import of peroxisomal matrix proteins. Peroxisomal matrix proteins are synthesized on free ribosomes in the cytosol and guided to the peroxisomal membrane by specific soluble receptors. At the membrane, the cargo-loaded receptors bind to a docking complex and the receptor-docking complex assembly is thought to form a dynamic pore which enables the transition of the cargo into the organellar lumen. The import cycle is completed by ubiquitination- and ATP-dependent dislocation of the receptor from the membrane to the cytosol, which is performed by the AAA-peroxins. Receptor ubiquitination and dislocation are the only energy-dependent steps in peroxisomal protein import. The export-driven import model suggests that the AAA-peroxins might function as motor proteins in peroxisomal import by coupling ATP-dependent removal of the peroxisomal import receptor and cargo translocation into the organelle. Pex6p might also have additional functions that appear not to be related to peroxisomes, yeast Pex6p acts as a suppressor for aging defects in mitochondria. Overexpression of Pex6p, but not of Pex1p, restores the import defect of mutant ATP2, the gene encoding the beta-subunit of mitochondrial F1,F0-ATPase, into mitochondria. Function for Pex6p in the prevention of necrotic cell death in yeast Saccharomyces cerevisiae
physiological function the enzyme is involved in peroxisome biogenesis abd associated with peroxisomal quality control. The Lon protease functions in the degradation of mutated or abnormal proteins as well as short-lived regulatory proteins, in particular those produced under stress conditions Escherichia coli
physiological function the enzyme is involved in peroxisome biogenesis and associated with peroxisomal quality control Penicillium chrysogenum
physiological function the enzyme is involved in peroxisome biogenesis and associated with peroxisomal quality control. Lon2 is required for the elimination of unnecessary proteins during the functional transition of glyoxysomes to peroxisomes Arabidopsis thaliana
physiological function the enzyme is involved in peroxisome biogenesis and associated with peroxisomal quality control. The peroxisomal Lon and autophagy function together in peroxisomal quality control Ogataea angusta