7NXD
Cryo-EM structure of human integrin alpha5beta1 in the half-bent conformation
Summary for 7NXD
Entry DOI | 10.2210/pdb7nxd/pdb |
Related | 3fcs 3vi3 4wk0 7NWL |
EMDB information | 12637 |
Descriptor | Integrin alpha-5, Integrin beta-1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total) |
Functional Keywords | integrin, cell adhesion, plasma membrane protein, a5b1, alpha5beta1, focal adhesion, half-bent conformation |
Biological source | Homo sapiens (Human) More |
Total number of polymer chains | 2 |
Total formula weight | 204742.42 |
Authors | Schumacher, S.,Dedden, D.,Vazquez Nunez, R.,Matoba, K.,Takagi, J.,Biertumpfel, C.,Mizuno, N. (deposition date: 2021-03-18, release date: 2021-08-25, Last modification date: 2024-10-23) |
Primary citation | Schumacher, S.,Dedden, D.,Nunez, R.V.,Matoba, K.,Takagi, J.,Biertumpfel, C.,Mizuno, N. Structural insights into integrin alpha 5 beta 1 opening by fibronectin ligand. Sci Adv, 7:-, 2021 Cited by PubMed Abstract: Integrin αβ is a major fibronectin receptor critical for cell migration. Upon complex formation, fibronectin and αβ undergo conformational changes. While this is key for cell-tissue connections, its mechanism is unknown. Here, we report cryo-electron microscopy structures of native human αβ with fibronectin to 3.1-angstrom resolution, and in its resting state to 4.6-angstrom resolution. The αβ-fibronectin complex revealed simultaneous interactions at the arginine-glycine-aspartate loop, the synergy site, and a newly identified binding site proximal to adjacent to metal ion-dependent adhesion site, inducing the translocation of helix α1 to secure integrin opening. Resting αβ adopts an incompletely bent conformation, challenging the model of integrin sharp bending inhibiting ligand binding. Our biochemical and structural analyses showed that affinity of αβ for fibronectin is increased with manganese ions (Mn) while adopting the half-bent conformation, indicating that ligand-binding affinity does not depend on conformation, and αβ opening is induced by ligand-binding. PubMed: 33962943DOI: 10.1126/sciadv.abe9716 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (4.6 Å) |
Structure validation
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