2VDN

Re-refinement of Integrin AlphaIIbBeta3 Headpiece Bound to Antagonist Eptifibatide

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2VDN の概要

• エントリーDOI: 10.2210/pdb2vdn/pdb
• 関連するPDBエントリー: 2VDK 2VDL 2VDM 2VDO 2VDP 2VDQ 2VDR
• 分子名称: INTEGRIN ALPHA-IIB, 2-acetamido-2-deoxy-beta-D-glucopyranose, MAGNESIUM ION, ... (12 entities in total)
• 機能のキーワード: cell adhesion-immune system complex, fibrinogen binding, platelet integrin alphaiibbeta3, glycoprotein, cell adhesion, membrane, integrin, receptor, antagonist, host-virus interaction, pyrrolidone carboxylic acid, transmembrane, phosphorylation, disease mutation, cleavage on pair of basic residues, cell adhesion/immune system
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 151190.67

構造登録者

Springer, T.A.,Zhu, J.,Xiao, T. (登録日: 2007-10-10, 公開日: 2008-09-02, 最終更新日: 2023-12-13)

主引用文献

Springer, T.A.,Zhu, J.,Xiao, T.
Structural Basis for Distinctive Recognition of Fibrinogen Gammac Peptide by the Platelet Integrin Alphaiibbeta3.
J.Cell Biol., 182:791-, 2008

PubMed Abstract: Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin alpha(IIb)beta(3) on platelets, resulting in platelet aggregation. alpha(v)beta(3) binds fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's alpha subunit. alpha(IIb)beta(3) also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the gamma subunit (gammaC peptide). These distinct modes of fibrinogen binding enable alpha(IIb)beta(3) and alpha(v)beta(3) to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin alpha(IIb)beta(3)-gammaC peptide interface, and, for comparison, integrin alpha(IIb)beta(3) bound to a lamprey gammaC primordial RGD motif. Compared with RGD, the GAKQAGDV motif in gammaC adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg(2+) ion binds the gammaC Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca(2+) ion binds the gammaC C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered gammaC peptide enhances our understanding of the involvement of gammaC peptide and integrin alpha(IIb)beta(3) in hemostasis and thrombosis.

PubMed: 18710925
DOI: 10.1083/JCB.200801146

実験手法

X-RAY DIFFRACTION (2.9 Å)