9E8C

Integrin aIIbb3 dimer conformation from human platelet membrane crude preparation

9E8C の概要

• エントリーDOI: 10.2210/pdb9e8c/pdb
• EMDBエントリー: 47716
• 分子名称: Integrin alpha-IIb, Integrin beta-3, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: platelet membrane protein integrin aiibb3, blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 406164.23

構造登録者

Han, X.,Nieman, M.T. (登録日: 2024-11-05, 公開日: 2025-10-15)

主引用文献

Han, X.,Zhang, Z.,Su, C.C.,Lyu, M.,Miyagi, M.,Yu, E.,Nieman, M.T.
Elucidating the dynamics of integrin alpha IIb beta 3 from native platelet membranes by cryo-EM with build-and-retrieve method.
Blood Adv, 9:4592-4606, 2025

PubMed Abstract: Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that affect the protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins to be solved from homogeneous samples. Our recent breakthroughs in data processing now make it feasible to obtain atomic-level-resolution protein structures from crude preparations in their native environments by integrating cryo-EM with the "build-and-retrieve" (BaR) data processing methodology. We applied this iterative bottom-up methodology on resting human platelet membranes for an in-depth systems biology approach to uncover how lipids, metal binding, post-translational modifications, and cofactor associations in the native environment regulate platelet function at the molecular level. Here, we report using cryo-EM followed by the BaR method to solve the unmodified integrin αIIbβ3 structure directly from resting human platelet membranes in its inactivated and intermediate states at 2.75 and 2.67 Å, respectively. Furthermore, we also solved a novel dimer conformation of αIIbβ3 at 2.85 Å formed by 2 intermediate states of αIIbβ3. This may indicate a previously unknown self-regulatory mechanism of αIIbβ3 in its native environment. In conclusion, our data show the power of using cryo-EM with the BaR method to determine 3 distinct structures including a novel dimer directly from natural sources. This approach allows us to identify unrecognized regulation mechanisms for proteins without artifacts owing to purification processes. These data have the potential to enrich our understanding of platelet signaling circuitry.

PubMed: 40472320
DOI: 10.1182/bloodadvances.2025016209

実験手法

ELECTRON MICROSCOPY (3 Å)