2h7o
From Proteopedia
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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 Thu Feb 21 17:39:01 2008
Categories: Single protein | Yersinia pseudotuberculosis | Bliska, J B. | Ivanov, M. | Prehna, G. | Stebbins, C E. | Gdi | Yersinia | Yopo | Ypka
