9E8B
Integrin aIIbb3 intermediate conformation from human platelet membrane crude preparation
Summary for 9E8B
| Entry DOI | 10.2210/pdb9e8b/pdb |
| EMDB information | 47715 |
| Descriptor | 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, ... (7 entities in total) |
| Functional Keywords | platelet membrane protein integrin aiibb3, blood clotting |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 123814.12 |
| Authors | |
| Primary citation | 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 Cited by 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: 40472320DOI: 10.1182/bloodadvances.2025016209 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.67 Å) |
Structure validation
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