9p6s | pdb_00009p6s

Cryo-EM structure of human integrin alpha5beta1 in complex with fibronectin (FN 7-10)

spinqualitylabelsall models 9p6s, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9p6s is a 3 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 2.61Å Ligands: BMA, MAN, MN, 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 The monoclonal antibody (mAb) TS2/16 stabilizes the active conformation of beta1 integrin, enhancing its adhesive capacity on the cell surface. However, the molecular mechanism by which TS2/16 modulates integrin affinity for extracellular ligands remains unclear. Using endogenous full-length alpha5beta1 integrin purified from human placenta, we determined the structure of integrin alpha5beta1 with fibronectin up to 2.61-A resolution in the absence of TS2/16, capturing the active form without its aid, and performed comparative B-factor-based analysis and CABS-Flex simulation with and without TS2/16. Despite no global conformational differences, we found that TS2/16 interacts with alpha2 helix of the integrin beta1 subunit and contacts the C-terminus of alpha3 helix, leading to a localized decrease in B factor. This interaction allosterically alters the dynamics of alpha2-alpha3 loop despite not being in direct contact with TS2/16. Notably, this loop directly engages fibronectin, and its dynamic change underlies the enhanced ligand-binding affinity and explains increased cell adhesion observed with TS2/16. These findings reveal an allosteric mechanism of integrin regulation by TS2/16 and offer insights for the rational design of therapeutic antibodies targeting integrin-mediated adhesion in pathological contexts such as inflammation and cancer. Allosteric regulation of fibronectin binding by the anti-beta1 integrin antibody TS2/16.,Ding J, Fantini DA, Dedden D, Schumacher S, Biertumpfel C, Mizuno N PNAS Nexus. 2026 Feb 24;5(3):pgag044. doi: 10.1093/pnasnexus/pgag044. eCollection , 2026 Mar. PMID:41809771 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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