5opy

Crystal structure of anti-alphaVbeta3 integrin Fab LM609

spinqualitylabelsall models 5opy, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5opy is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.26Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The LM609 antibody specifically recognizes alphaVbeta3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for alphaVbeta3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of alphaVbeta3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for alphaVbeta3. Using single-particle electron microscopy, we show that LM609 binds at the interface between the beta-propeller domain of the alphaV chain and the betaI domain of the beta3 chain, near the RGD-binding site, of all observed integrin conformational states. Integrating these data with fluorescence size-exclusion chromatography, we demonstrate that LM609 sterically hinders access of large ligands to the RGD-binding pocket, without obstructing it. This work provides a structural framework to expedite future efforts utilizing LM609 as a diagnostic or therapeutic tool. The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human alphaVbeta3 Integrin via Steric Hindrance.,Borst AJ, James ZM, Zagotta WN, Ginsberg M, Rey FA, DiMaio F, Backovic M, Veesler D Structure. 2017 Oct 7. pii: S0969-2126(17)30298-8. doi:, 10.1016/j.str.2017.09.007. PMID:29033288 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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