2H7V

Co-crystal structure of YpkA-Rac1

Summary for 2H7V

• Entry DOI: 10.2210/pdb2h7v/pdb
• Related: 2H7O
• Descriptor: Migration-inducing protein 5, Protein kinase ypkA, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: ypka, yopo, rac1, gdi, gtpase, yersinia, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity): P63000; Secreted: Q05608
• Total number of polymer chains: 4
• Total formula weight: 111411.29

Authors

Prehna, G.,Ivanov, M.,Bliska, J.B.,Stebbins, C.E. (deposition date: 2006-06-04, release date: 2006-09-19, Last modification date: 2023-08-30)

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 (2.6 Å)