3NIG

The Closed Headpiece of Integrin IIb 3 and its Complex with an IIb 3 -Specific Antagonist That Does Not Induce Opening

3NIG の概要

• エントリーDOI: 10.2210/pdb3nig/pdb
• 関連するPDBエントリー: 2VDR 3NID 3NIF
• 分子名称: Integrin alpha-IIb, MAGNESIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• 機能のキーワード: integrin, headpiece, alphaiib, beta3, cell adhesion-immune system complex, cell adhesion-blood clotting complex, cell adhesion/blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 300994.33

構造登録者

Zhu, J.H.,Zhu, J.Q.,Springer, T.A. (登録日: 2010-06-15, 公開日: 2010-12-22, 最終更新日: 2024-11-27)

主引用文献

Zhu, J.,Zhu, J.,Negri, A.,Provasi, D.,Filizola, M.,Coller, B.S.,Springer, T.A.
Closed headpiece of integrin {alpha}IIb{beta}3 and its complex with an {alpha}IIb{beta}3-specific antagonist that does not induce opening.
Blood, 116:5050-5059, 2010

PubMed Abstract: The platelet integrin α(IIb)β(3) is essential for hemostasis and thrombosis through its binding of adhesive plasma proteins. We have determined crystal structures of the α(IIb)β(3) headpiece in the absence of ligand and after soaking in RUC-1, a novel small molecule antagonist. In the absence of ligand, the α(IIb)β(3) headpiece is in a closed conformation, distinct from the open conformation visualized in presence of Arg-Gly-Asp (RGD) antagonists. In contrast to RGD antagonists, RUC-1 binds only to the α(IIb) subunit. Molecular dynamics revealed nearly identical binding. Two species-specific residues, α(IIb) Y190 and α(IIb) D232, in the RUC-1 binding site were confirmed as important by mutagenesis. In sharp contrast to RGD-based antagonists, RUC-1 did not induce α(IIb)β(3) to adopt an open conformation, as determined by gel filtration and dynamic light scattering. These studies provide insights into the factors that regulate integrin headpiece opening, and demonstrate the molecular basis for a novel mechanism of integrin antagonism.

PubMed: 20679525
DOI: 10.1182/blood-2010-04-281154

実験手法

X-RAY DIFFRACTION (2.25 Å)