7nxd

Cryo-EM structure of human integrin alpha5beta1 in the half-bent conformation

spinqualitylabelsall models 7nxd, resolution 4.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nxd is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.6Å Ligands: BMA, CA, MAN, MG, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ITA5_HUMAN Integrin alpha-5/beta-1 is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. Publication Abstract from PubMed Integrin alpha(5)beta(1) is a major fibronectin receptor critical for cell migration. Upon complex formation, fibronectin and alpha(5)beta(1) 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 alpha(5)beta(1) with fibronectin to 3.1-angstrom resolution, and in its resting state to 4.6-angstrom resolution. The alpha(5)beta(1)-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 alpha1 to secure integrin opening. Resting alpha(5)beta(1) adopts an incompletely bent conformation, challenging the model of integrin sharp bending inhibiting ligand binding. Our biochemical and structural analyses showed that affinity of alpha(5)beta(1) for fibronectin is increased with manganese ions (Mn(2+)) while adopting the half-bent conformation, indicating that ligand-binding affinity does not depend on conformation, and alpha(5)beta(1) opening is induced by ligand-binding. Structural insights into integrin alpha(5)beta(1) opening by fibronectin ligand.,Schumacher S, Dedden D, Nunez RV, Matoba K, Takagi J, Biertumpfel C, Mizuno N Sci Adv. 2021 May 7;7(19):eabe9716. doi: 10.1126/sciadv.abe9716. Print 2021 May. PMID:33962943 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Integrin 3D structures

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