8GCE

The Extracellular Domain of Integrin AlphaIIbBeta3 in Intermediate State

Summary for 8GCE

• Entry DOI: 10.2210/pdb8gce/pdb
• EMDB information: 29932
• 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: integrin, cell adhesion
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 202928.98

Authors

Huo, T.,Wu, H.,Wang, Z. (deposition date: 2023-03-01, release date: 2024-03-06, Last modification date: 2025-05-21)

Primary citation

Huo, T.,Wu, H.,Moussa, Z.,Sen, M.,Dalton, V.,Wang, Z.
Full-length alpha IIb beta 3 cryo-EM structure reveals intact integrin initiate-activation intrinsic architecture.
Structure, 32:899-, 2024

PubMed Abstract: Integrin αIIbβ3 is the key receptor regulating platelet retraction and accumulation and a proven drug-target for antithrombotic therapies. Here we resolve the cryo-EM structures of the full-length αIIbβ3, which covers three distinct states along the activation pathway. Firstly, we obtain the αIIbβ3 structure at 3 Å resolution in the inactive state, revealing the overall topology of the heterodimer with the transmembrane (TM) helices and the ligand-binding domain tucked in a specific angle proximity to the TM region. After the addition of a Mn agonist, we resolve two coexisting structures representing two new states between inactive and active state. Our structures show conformational changes of the αIIbβ3 activating trajectory and a unique twisting of the integrin legs, which is required for platelets accumulation. Our structure provides direct structural evidence for how the lower legs are involved in full-length integrin activation mechanisms and offers a new strategy to target the αIIbβ3 lower leg.

PubMed: 38579706
DOI: 10.1016/j.str.2024.03.006

Experimental method

ELECTRON MICROSCOPY (3.12 Å)