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The Rho GTPase inactivation domain in Vibrio cholerae MARTX toxin has a circularly permuted papain‐like thiol protease fold
Author(s) -
Pei Jimin,
Grishin Nick V.
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22447
Subject(s) - vibrio cholerae , shigella flexneri , biology , virulence , gtpase , proteases , rhoa , microbiology and biotechnology , biochemistry , genetics , escherichia coli , gene , bacteria , signal transduction , enzyme
A Rho GTPase inactivation domain (RID) has been discovered in the multifunctional, autoprocessing RTX toxin RtxA from Vibrio cholerae . The RID domain causes actin depolymerization and rounding of host cells through inactivation of the small Rho GTPases Rho, Rac, and Cdc42. With only a few toxin proteins containing RID domains in the current sequence database, the structure and molecular mechanisms of this domain are unknown. Using comparative sequence and structural analyses, we report homology inference, fold recognition, and active site prediction for RID domains. Remote homologs of RID domains were identified in two other experimentally characterized bacterial virulence factors: IcsB of Shigella flexneri and BopA of Burkholderia pseudomallei , as well as in a group of uncharacterized bacterial membrane proteins. IcsB plays an important role in helping Shigella to evade the host autophagy defense system. RID domain homologs share a conserved diad of cysteine and histidine residues, and are predicted to adopt a circularly permuted papain‐like thiol protease fold. RID domains from MARTX toxins and virulence factors IcsB and BopA thus could function as proteases or acyltransferases acting on host molecules. Our results provide structural and mechanistic insights into several important proteins functioning in bacterial pathogenesis. Proteins 2009. © 2009 Wiley‐Liss, Inc.