1AUQ

A1 DOMAIN OF VON WILLEBRAND FACTOR

1AUQ の概要

• エントリーDOI: 10.2210/pdb1auq/pdb
• 分子名称: A1 DOMAIN OF VON WILLEBRAND FACTOR, CADMIUM ION (3 entities in total)
• 機能のキーワード: willebrand, blood coagulation, platelet, glycoprotein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P04275
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23872.92

構造登録者

Emsley, J.,Cruz, M.,Handin, R.,Liddington, R. (登録日: 1997-09-01, 公開日: 1998-10-14, 最終更新日: 2024-10-23)

主引用文献

Emsley, J.,Cruz, M.,Handin, R.,Liddington, R.
Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib.
J.Biol.Chem., 273:10396-10401, 1998

PubMed Abstract: von Willebrand Factor (vWF) is a multimeric protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury under conditions of high flow/shear. The A1 domain of vWF (vWF-A1) forms the principal binding site for platelet glycoprotein Ib (GpIb), an interaction that is tightly regulated. We report here the crystal structure of the vWF-A1 domain at 2.3-A resolution. As expected, the overall fold is similar to that of the vWF-A3 and integrin I domains. However, the structure also contains N- and C-terminal arms that wrap across the lower surface of the domain. Unlike the integrin I domains, vWF-A1 does not contain a metal ion-dependent adhesion site motif. Analysis of the available mutagenesis data suggests that the activator botrocetin binds to the right-hand face of the domain containing helices alpha5 and alpha6. Possible binding sites for GpIb are the front and upper surfaces of the domain. Natural mutations that lead to constitutive GpIb binding (von Willebrand type IIb disease) cluster in a different site, at the interface between the lower surface and the terminal arms, suggesting that they disrupt a regulatory region rather than forming part of the primary GpIb binding site. A possible pathway for propagating structural changes from the regulatory region to the ligand-binding surface is discussed.

PubMed: 9553097
DOI: 10.1074/jbc.273.17.10396

実験手法

X-RAY DIFFRACTION (2.3 Å)