7NWL

Cryo-EM structure of human integrin alpha5beta1 (open form) in complex with fibronectin and TS2/16 Fv-clasp

Summary for 7NWL

• Entry DOI: 10.2210/pdb7nwl/pdb
• Related: 1fnf 3vi3 4wk0 5cxc 7NXD
• EMDB information: 12634
• Descriptor: Integrin alpha-5, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, MANGANESE (II) ION, ... (11 entities in total)
• Functional Keywords: integrin, fibronectin, ts2/16, cell adhesion, plasma membrane protein, a5b1, alpha5beta1, focal adhesion, open conformation
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 280943.50

Authors

Schumacher, S.,Dedden, D.,Vazquez Nunez, R.,Matoba, K.,Takagi, J.,Biertumpfel, C.,Mizuno, N. (deposition date: 2021-03-17, release date: 2021-06-02, Last modification date: 2024-11-13)

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

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: 33962943
DOI: 10.1126/sciadv.abe9716

Experimental method

ELECTRON MICROSCOPY (3.1 Å)