Many questions about the significance of structural features of integrin ?(V)?(3) with respect to its mechanism of activation remain. We have determined and re-refined crystal structures of the ?(V)?(3) ectodomain linked to C-terminal coiled coils (?(V)?(3)-AB) and four transmembrane (TM) residues in each subunit (?(V)?(3)-1TM), respectively. The ?(V) and ?(3) subunits with four and eight extracellular domains, respectively, are bent at knees between the integrin headpiece and lower legs, and the headpiece has the closed, low-affinity conformation. The structures differ in the occupancy of three metal-binding sites in the ?I domain. Occupancy appears to be related to the pH of crystallization, rather than to the physiologic regulation of ligand binding at the central, metal ion-dependent adhesion site. No electron density was observed for TM residues and much of the ?(V) linker. ?(V)?(3)-AB and ?(V)?(3)-1TM demonstrate flexibility in the linker between their extracellular and TM domains, rather than the previously proposed rigid linkage. A previously postulated interface between the ?(V) and ?(3) subunits at their knees was also not supported, because it lacks high-quality density, required rebuilding in ?(V)?(3)-1TM, and differed markedly between ?(V)?(3)-1TM and ?(V)?(3)-AB. Together with the variation in domain-domain orientation within their bent ectodomains between ?(V)?(3)-AB and ?(V)?(3)-1TM, these findings are compatible with the requirement for large structural changes, such as extension at the knees and headpiece opening, in conveying activation signals between the extracellular ligand-binding site and the cytoplasm.