1FE8

CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR A3 DOMAIN IN COMPLEX WITH A FAB FRAGMENT OF IGG RU5 THAT INHIBITS COLLAGEN BINDING

1FE8 の概要

• エントリーDOI: 10.2210/pdb1fe8/pdb
• 関連するPDBエントリー: 1AO3 1ATZ
• 分子名称: VON WILLEBRAND FACTOR, IMMUNOGLOBULIN IGG RU5, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: collagen binding, conformational changes, epitope, von willebrand factor a-type domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 201594.32

構造登録者

Bouma, B.,Huizinga, E.G.,Schiphorst, M.E.,Sixma, J.J.,Kroon, J.,Gros, P. (登録日: 2000-07-21, 公開日: 2001-04-04, 最終更新日: 2024-10-16)

主引用文献

Romijn, R.A.,Bouma, B.,Wuyster, W.,Gros, P.,Kroon, J.,Sixma, J.J.,Huizinga, E.G.
Identification of the collagen-binding site of the von Willebrand factor A3-domain.
J.Biol.Chem., 276:9985-9991, 2001

PubMed Abstract: Von Willebrand factor (vWF) is a multimeric glycoprotein that mediates platelet adhesion and thrombus formation at sites of vascular injury. vWF functions as a molecular bridge between collagen and platelet receptor glycoprotein Ib. The major collagen-binding site of vWF is contained within the A3 domain, but its precise location is unknown. To localize the collagen-binding site, we determined the crystal structure of A3 in complex with an Fab fragment of antibody RU5 that inhibits collagen binding. The structure shows that RU5 recognizes a nonlinear epitope consisting of residues 962-966, 981-997, and 1022-1026. Alanine mutants were constructed of residues Arg(963), Glu(987), His(990), Arg(1016), and His(1023), located in or close to the epitope. Mutants were expressed as fully processed multimeric vWF. Mutation of His(1023) abolished collagen binding, whereas mutation of Arg(963) and Arg(1016) reduced collagen binding by 25-35%. These residues are part of loops alpha3beta4 and alpha1beta2 and alpha-helix 3, respectively, and lie near the bottom face of the domain. His(1023) and flanking residues display multiple conformations in available A3-crystal structures, suggesting that binding of A3 to collagen involves an induced-fit mechanism. The collagen-binding site of A3 is located distant from the top face of the domain where collagen-binding sites are found in homologous integrin I domains.

PubMed: 11098050
DOI: 10.1074/jbc.M006548200

実験手法

X-RAY DIFFRACTION (2.03 Å)