1XXV

Yersinia YopH (residues 163-468) binds phosphonodifluoromethyl-Phe containing hexapeptide at two sites

1XXV の概要

• エントリーDOI: 10.2210/pdb1xxv/pdb
• 関連するPDBエントリー: 1QZ0 1XXP
• 分子名称: Protein-tyrosine phosphatase yopH, Epidermal growth factor receptor derived peptide (3 entities in total)
• 機能のキーワード: catalytic domain, phosphotyrosine-binding sites, substrate targeting, hydrolase
• 由来する生物種: Yersinia enterocolitica; 詳細
• 細胞内の位置: Secreted: P15273
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 70490.60

構造登録者

Ivanov, M.I.,Stuckey, J.A.,Schubert, H.L.,Saper, M.A.,Bliska, J.B. (登録日: 2004-11-08, 公開日: 2005-03-22, 最終更新日: 2024-11-20)

主引用文献

Ivanov, M.I.,Stuckey, J.A.,Schubert, H.L.,Saper, M.A.,Bliska, J.B.
Two substrate-targeting sites in the Yersinia protein tyrosine phosphatase co-operate to promote bacterial virulence
Mol.Microbiol., 55:1346-1356, 2005

PubMed Abstract: YopH is a protein tyrosine phosphatase and an essential virulence determinant of the pathogenic bacterium Yersinia. Yersinia delivers YopH into infected host cells using a type III secretion mechanism. YopH dephosphorylates several focal adhesion proteins including p130Cas in human epithelial cells, resulting in disruption of focal adhesions and cell detachment from the extracellular matrix. How the C-terminal protein tyrosine phosphatase domain of YopH targets specific substrates such as p130Cas in the complex milieu of the host cell has not been fully elucidated. An N-terminal non-catalytic domain of YopH binds p130Cas in a phosphotyrosine-dependent manner and functions as a novel substrate-targeting site. The structure of the YopH protein tyrosine phosphatase domain bound to a model phosphopeptide substrate was solved and the resulting structure revealed a second substrate-targeting site ('site 2') within the catalytic domain. Site 2 binds to p130Cas in a phosphotyrosine-dependent manner, and co-operates with the N-terminal domain ('site 1') to promote efficient recognition of p130Cas by YopH in epithelial cells. The identification of two substrate-targeting sites in YopH that co-operate to promote epithelial cell detachment and bacterial virulence reinforces the importance of protein-protein interactions for determining protein tyrosine phosphatase specificity in vivo, and highlights the sophisticated nature of microbial pathogenicity factors.

PubMed: 15720545
DOI: 10.1111/j.1365-2958.2005.04477.x

実験手法

X-RAY DIFFRACTION (2.5 Å)