2h7v
From Proteopedia
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Co-crystal structure of YpkA-Rac1
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
2H7V is a Protein complex structure of sequences from Homo sapiens and Yersinia pseudotuberculosis with and as ligands. 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 17:39:06 2008
Categories: Homo sapiens | Protein complex | Yersinia pseudotuberculosis | Bliska, J B. | Ivanov, M. | Prehna, G. | Stebbins, C E. | GDP | MG | Gdi | Gtpase | Rac1 | Yersinia | Yopo | Ypka
