1U0N

The ternary von Willebrand Factor A1-glycoprotein Ibalpha-botrocetin complex

1U0N の概要

• エントリーDOI: 10.2210/pdb1u0n/pdb
• 関連するPDBエントリー: 1AUQ 1IJB 1IJK
• 分子名称: Von Willebrand factor, Botrocetin, Platelet glycoprotein Ib, ... (4 entities in total)
• 機能のキーワード: rossmann fold, lrr motif, c-type lectin fold, protein-protein complex, blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P04275 P22029 P22030; Membrane; Single-pass type I membrane protein: P07359
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83531.42

構造登録者

Fukuda, K.,Liddington, R.C. (登録日: 2004-07-13, 公開日: 2005-04-19, 最終更新日: 2024-10-30)

主引用文献

Fukuda, K.,Doggett, T.,Laurenzi, I.J.,Liddington, R.C.,Diacovo, T.G.
The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation
Nat.Struct.Mol.Biol., 12:152-159, 2005

PubMed Abstract: Botrocetin is a snake venom protein that enhances the affinity of the A1 domain of plasma von Willebrand factor (vWF) for the platelet receptor glycoprotein Ibalpha (GPIbalpha), an event that contributes to bleeding and host death. Here we describe a kinetic and crystallographic analysis of this interaction that reveals a novel mechanism of affinity enhancement. Using high-temporal-resolution microscopy, we show that botrocetin decreases the GPIbalpha off-rate two-fold in both human and mouse complexes without affecting the on-rate. The key to this behavior is that, upon binding of GPIbalpha to vWF-A1, botrocetin prebound to vWF-A1 makes no contacts initially with GPIbalpha, but subsequently slides around the A1 surface to form a new interface. This two-step mechanism and flexible coupling may prevent adverse alterations in on-rate of GPIbalpha for vWF-A1, and permit adaptation to structural differences in GPIbalpha and vWF in several prey species.

PubMed: 15665869
DOI: 10.1038/nsmb892

実験手法

X-RAY DIFFRACTION (2.95 Å)