2H7O

Crystal structure of the Rho-GTPase binding domain of YpkA

2H7O の概要

• エントリーDOI: 10.2210/pdb2h7o/pdb
• 分子名称: Protein kinase ypkA (2 entities in total)
• 機能のキーワード: ypka, yopo, yersinia, gdi, signaling protein
• 由来する生物種: Yersinia pseudotuberculosis
• 細胞内の位置: Secreted: Q05608
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34449.02

構造登録者

Prehna, G.,Ivanov, M.,Bliska, J.B.,Stebbins, C.E. (登録日: 2006-06-02, 公開日: 2006-09-19, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)