The LM609 antibody specifically recognizes αβ 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 αβ-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αβ integrin， we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αβ. Using single-particle electron microscopy， we show that LM609 binds at the interface between the β-propeller domain of the α chain and the βI domain of the β 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.