2GI7

Crystal structure of human platelet Glycoprotein VI (GPVI)

2GI7 の概要

• エントリーDOI: 10.2210/pdb2gi7/pdb
• 分子名称: GPVI protein, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: ig-like domains, blood clotting, cell adhesion
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40811.44

構造登録者

Horii, K.,Kahn, M.L.,Herr, A.B. (登録日: 2006-03-28, 公開日: 2007-04-03, 最終更新日: 2024-11-06)

主引用文献

Horii, K.,Kahn, M.L.,Herr, A.B.
Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI.
Blood, 108:936-942, 2006

PubMed Abstract: Activation of circulating platelets by exposed vessel wall collagen is a primary step in the pathogenesis of heart attack and stroke, and drugs to block platelet activation have successfully reduced cardiovascular morbidity and mortality. In humans and mice, collagen activation of platelets is mediated by glycoprotein VI (GPVI), a receptor that is homologous to immune receptors but bears little sequence similarity to known matrix protein adhesion receptors. Here we present the crystal structure of the collagen-binding domain of human GPVI and characterize its interaction with a collagen-related peptide. Like related immune receptors, GPVI contains 2 immunoglobulin-like domains arranged in a perpendicular orientation. Significantly, GPVI forms a back-to-back dimer in the crystal, an arrangement that could explain data previously obtained from cell-surface GPVI inhibition studies. Docking algorithms identify 2 parallel grooves on the GPVI dimer surface as collagen-binding sites, and the orientation and spacing of these grooves precisely match the dimensions of an intact collagen fiber. These findings provide a structural basis for the ability of an immune-type receptor to generate signaling responses to collagen and for the development of GPVI inhibitors as new therapies for human cardiovascular disease.

PubMed: 16861347
DOI: 10.1182/blood-2006-01-010215

実験手法

X-RAY DIFFRACTION (2.4 Å)