6BXB

Crystal structure of an extended b3 integrin P33

6BXB の概要

• エントリーDOI: 10.2210/pdb6bxb/pdb
• 関連するPDBエントリー: 6BXF 6BXJ
• 分子名称: Chimera protein of Integrin beta-3 and Integrin alpha-L, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: integrin, cell adhesion
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 105259.99

構造登録者

Zhou, D.,Zhu, J. (登録日: 2017-12-18, 公開日: 2018-08-01, 最終更新日: 2024-11-06)

主引用文献

Zhou, D.,Thinn, A.M.M.,Zhao, Y.,Wang, Z.,Zhu, J.
Structure of an extended beta3integrin.
Blood, 132:962-972, 2018

PubMed Abstract: Cells use adhesion receptor integrins to communicate with their surroundings. Integrin activation and cellular signaling are coupled with change from bent to extended conformation. β integrins, including αβ, which is essential for the function of platelets in hemostasis and thrombosis, and αβ, which plays multiple roles in diverse cell types, have been prototypes in understanding integrin structure and function. Despite extensive structural studies, a high-resolution integrin structure in an extended conformation remains to be determined. The human β Leu33Pro polymorphism, located at the PSI domain, defines human platelet-specific alloantigens 1a and 1b (HPA-1a/b), immune response to which is a cause of posttransfusion purpura and fetal/neonatal alloimmune thrombocytopenia. Leu33Pro substitution has also been suggested to be a risk factor for thrombosis. Here we report the crystal structure of the β headpiece in either Leu33 or Pro33 form, both of which reveal intermediate and fully extended conformations coexisting in 1 crystal. These were used to build high-resolution structures of full-length β integrin in the intermediate and fully extended states, agreeing well with the corresponding conformations observed by electron microscopy. Our structures reveal how β integrin becomes extended at its β-knee region and how the flexibility of β-leg domains is determined. In addition, our structures reveal conformational changes of the PSI and I-EGF1 domains upon β extension, which may affect the binding of conformation-dependent anti-HPA-1a alloantibodies. Our structural and functional data show that Leu33Pro substitution does not directly alter the conformation or ligand binding of β integrin.

PubMed: 30018079
DOI: 10.1182/blood-2018-01-829572

実験手法

X-RAY DIFFRACTION (2.39 Å)