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Literature summary for 3.4.22.64 extracted from

  • Li, Z.; Liu, W.; Fu, J.; Cheng, S.; Xu, Y.; Wang, Z.; Liu, X.; Shi, X.; Liu, Y.; Qi, X.; Liu, X.; Ding, J.; Shao, F.
    Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11 (2021), Nature, 599, 290-295.
    View publication on PubMed
Search for more literature for 3.4.22.64

Cloned(Commentary)

Cloned (Comment) Organism
gene CASP4, recombinant expression of wild-type and mutant enzymes in HEK-293T cells Mus musculus

Protein Variants

Protein Variants Comment Organism
C254A site-directed mutagenesis, OspC3 also co-immunoprecipitated with inactive p20- and-p10-unprocessed caspase-11 Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Mus musculus 5829
-

Organism

Organism UniProt Comment Textmining
Mus musculus P70343 cf. caspase-4, EC 3.4.22.57
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Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification caspase-11 performs LPS-induced autoprocessing to activate itself. Mutations of Arg310 inhibit infection- or LPS-induced pyroptosis Mus musculus
side-chain modification arginine ADP-riboxanase OspC3 catalyses ADP-riboxanation on arginine 310 in caspase-11. A 17-Da loss occurs on the phosphoribosylated arginine caused by non-specific pyrophosphohydrolase, NUDT16, which removes an AMP from OspC3-modified caspase-11. Deamino-NAD+, biotin-NAD+, epsilon-NAD+ or nicotinamide guanine dinucleotide (NGD+) allow modifications that preserve the mass difference between the cognate analogue and NAD+ confirming the transfer of ADPR to caspase-11 with Nam being the leaving group. OspC3 modifies Arg310 of caspase-11 by two steps. First, the arginine Ndelta (rather than Nomega) performs nucleophilic substitution of the Nam in NAD+. Second, the ribosyl-2'-OH of ADPR initiates a deamination to remove one Nomega, forming an oxazolidine ring. Although OspC3(D177A) mutant-modified caspase-11 is sensitive to ADP-ribosylarginine hydrolase (ADPRH), wild-type OspC3-catalysed ADP-riboxanation resists demodification by ADPRH and other known host ADP-ribosylhydrolases. OspC3 blocks LPS-induced caspase-11 autoprocessing Mus musculus

General Information

General Information Comment Organism
malfunction ADP-riboxanation of the Arg310 in caspase-11 blocks autoprocessing of caspase-11 as well as its recognition and cleavage of gasdermin D (GSDMD). ADP-riboxanation of caspase-11 paralyses pyroptosis-mediated defence in Shigella-infected mice. Mutation of ospC3 stimulates caspase-11- and GSDMD-dependent anti-Shigella humoral immunity, generating a vaccine-like protective effect Mus musculus
metabolism ADP-riboxanation of a specific arginine residue in caspase-11/4 is a bacterial virulence mechanism that prevents LPS-induced pyroptosis Mus musculus
physiological function mouse caspase-11 recognizes cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein gasdermin D, GSDMD. This non-canonical inflammasome defends against Gram-negative bacteria. But, in contrast to infection with the cytosolic bacterium Burkholderia thailandensis, caspase-11 does not protect mice from infection with Shigella flexneri, which lives freely within the host cytosol where the inflammatory caspases reside. Shigella flexneri evades pyroptosis mediated by caspase-11 using a type III secretion system (T3SS) effector, OspC3. OspC3, but not its paralogues OspC1 and 2, covalently modifies caspase-11. Although it uses the NAD+ donor, this modification is not ADP-ribosylation, but an ADP-riboxanation modification on Arg310 in caspase-11 Mus musculus