1IJB

The von Willebrand Factor mutant (I546V) A1 domain

1IJB の概要

• エントリーDOI: 10.2210/pdb1ijb/pdb
• 関連するPDBエントリー: 1AUQ 1IJK
• 分子名称: von Willebrand factor (2 entities in total)
• 機能のキーワード: dinucleotide-binding fold, blood clotting
• 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: 23125.79

構造登録者

Fukuda, K.,Doggett, T.A.,Bankston, L.A.,Cruz, M.A.,Diacovo, T.G.,Liddington, R.C. (登録日: 2001-04-25, 公開日: 2002-07-10, 最終更新日: 2024-10-30)

主引用文献

Fukuda, K.,Doggett, T.A.,Bankston, L.A.,Cruz, M.A.,Diacovo, T.G.,Liddington, R.C.
Structural basis of von Willebrand factor activation by the snake toxin botrocetin.
Structure, 10:943-950, 2002

PubMed Abstract: The A1 domain of von Willebrand factor (vWF) mediates platelet adhesion to sites of vascular injury by binding to the platelet receptor glycoprotein Ib (GpIb), an interaction that is regulated by hydrodynamic shear forces. The GpIb binding surface of A1 is distinct from a regulatory region, suggesting that ligand binding is controlled allosterically. Here we report the crystal structures of the "gain-of-function" mutant A1 domain (I546V) and its complex with the exogenous activator botrocetin. We show that botrocetin switches the mutant A1 back toward the wild-type conformation, suggesting that affinity is enhanced by augmenting the GpIb binding surface rather than through allosteric control. Functional studies of platelet adhesion under flow further suggest that the activation mechanism is distinct from that of the gain-of-function mutation.

PubMed: 12121649
DOI: 10.1016/S0969-2126(02)00787-6

実験手法

X-RAY DIFFRACTION (1.8 Å)