3GXB

Crystal structure of VWF A2 domain

3GXB の概要

• エントリーDOI: 10.2210/pdb3gxb/pdb
• 分子名称: von Willebrand factor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: vwa-like fold, blood coagulation, cell adhesion, cleavage on pair of basic residues, disease mutation, disulfide bond, extracellular matrix, glycoprotein, hemostasis, isopeptide bond, secreted, von willebrand disease
• 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: 43020.08

構造登録者

Zhou, Y.F.,Springer, T.A. (登録日: 2009-04-02, 公開日: 2009-05-05, 最終更新日: 2024-11-06)

主引用文献

Zhang, Q.,Zhou, Y.F.,Zhang, C.Z.,Zhang, X.,Lu, C.,Springer, T.A.
Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor.
Proc.Natl.Acad.Sci.USA, 106:9226-9231, 2009

PubMed Abstract: The lengths of von Willebrand factor (VWF) concatamers correlate with hemostatic potency. After secretion in plasma, length is regulated by hydrodynamic shear force-dependent unfolding of the A2 domain, which is then cleaved by a specific protease. The 1.9-A crystal structure of the A2 domain demonstrates evolutionary adaptations to this shear sensor function. Unique among VWF A (VWA) domains, A2 contains a loop in place of the alpha4 helix, and a cis-proline. The central beta4-strand is poorly packed, with multiple side-chain rotamers. The Tyr-Met cleavage site is buried in the beta4-strand in the central hydrophobic core, and the Tyr structurally links to the C-terminal alpha6-helix. The alpha6-helix ends in 2 Cys residues that are linked by an unusual vicinal disulfide bond that is buried in a hydrophobic pocket. These features may narrow the force range over which unfolding occurs and may also slow refolding. Von Willebrand disease mutations, which presumably lower the force at which A2 unfolds, are illuminated by the structure.

PubMed: 19470641
DOI: 10.1073/pnas.0903679106

実験手法

X-RAY DIFFRACTION (1.9 Å)