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TitleStructural insights into integrin αβ opening by fibronectin ligand.
Journal, issue, pagesSci Adv, Vol. 7, Issue 19, Year 2021
Publish dateMay 7, 2021
AuthorsStephanie Schumacher / Dirk Dedden / Roberto Vazquez Nunez / Kyoko Matoba / Junichi Takagi / Christian Biertümpfel / Naoko Mizuno /
PubMed AbstractIntegrin 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, ...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.
External linksSci Adv / PubMed:33962943 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.6 Å
Structure data

EMDB-12634, PDB-7nwl:
Cryo-EM structure of human integrin alpha5beta1 (open form) in complex with fibronectin and TS2/16 Fv-clasp
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-12637, PDB-7nxd:
Cryo-EM structure of human integrin alpha5beta1 in the half-bent conformation
Method: EM (single particle) / Resolution: 4.6 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • Human (human)
  • mus musculus (house mouse)
KeywordsCELL ADHESION / integrin / fibronectin / TS2/16 / plasma membrane protein / a5b1 / alpha5beta1 / focal adhesion / open conformation / half-bent conformation

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