2H7O

Crystal structure of the Rho-GTPase binding domain of YpkA

Summary for 2H7O

• Entry DOI: 10.2210/pdb2h7o/pdb
• Descriptor: Protein kinase ypkA (2 entities in total)
• Functional Keywords: ypka, yopo, yersinia, gdi, signaling protein
• Biological source: Yersinia pseudotuberculosis
• Cellular location: Secreted: Q05608
• Total number of polymer chains: 1
• Total formula weight: 34449.02

Authors

Prehna, G.,Ivanov, M.,Bliska, J.B.,Stebbins, C.E. (deposition date: 2006-06-02, release date: 2006-09-19, Last modification date: 2024-02-14)

Primary citation

Prehna, G.,Ivanov, M.I.,Bliska, J.B.,Stebbins, C.E.
Yersinia virulence depends on mimicry of host rho-family nucleotide dissociation inhibitors.
Cell(Cambridge,Mass.), 126:869-880, 2006

PubMed Abstract: 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.

PubMed: 16959567
DOI: 10.1016/j.cell.2006.06.056

Experimental method

X-RAY DIFFRACTION (2 Å)