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'''Crystal structure of the Rho-GTPase binding domain of YpkA''' | '''Crystal structure of the Rho-GTPase binding domain of YpkA''' | ||
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[[Category: Prehna, G.]] | [[Category: Prehna, G.]] | ||
[[Category: Stebbins, C E.]] | [[Category: Stebbins, C E.]] | ||
[[Category: | [[Category: Gdi]] | ||
[[Category: | [[Category: Yersinia]] | ||
[[Category: | [[Category: Yopo]] | ||
[[Category: | [[Category: Ypka]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:58:03 2008'' | |||
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Revision as of 02:58, 4 May 2008
Crystal structure of the Rho-GTPase binding domain of YpkA
Overview
Yersinia spp. cause gastroenteritis and the plague, representing historically devastating pathogens that are currently an important biodefense and antibiotic resistance concern. A critical virulence determinant is the Yersinia protein kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide exchange in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface abolish this activity in vitro and impair in vivo YpkA-induced cytoskeletal disruption. In cell culture experiments, the kinase and the GDI domains of YpkA act synergistically to promote cytoskeletal disruption, and a Y. pseudotuberculosis mutant lacking YpkA GDI activity shows attenuated virulence in a mouse infection assay. We conclude that virulence in Yersinia depends strongly upon mimicry of host GDI proteins by YpkA.
About this Structure
2H7O is a Single protein structure of sequence from Yersinia pseudotuberculosis. Full crystallographic information is available from OCA.
Reference
Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors., Prehna G, Ivanov MI, Bliska JB, Stebbins CE, Cell. 2006 Sep 8;126(5):869-80. PMID:16959567 Page seeded by OCA on Sun May 4 05:58:03 2008
