Distinct recognition of complement iC3b by integrins αXβ2 and αMβ2.

Recognition by the leukocyte integrins α_Xβ₂ and α_Mβ₂ of complement iC3b-opsonized targets is essential for effector functions including phagocytosis. The integrin-binding sites on iC3b remain incompletely characterized. Here, we describe negative-stain electron microscopy and biochemical studies of α_Xβ₂ and α_Mβ₂ in complex with iC3b. Despite high homology, the two integrins bind iC3b at multiple distinct sites. α_Xβ₂ uses the α_X αI domain to bind iC3b on its C3c moiety at one of two sites: a major site at the interface between macroglobulin (MG) 3 and MG4 domains, and a less frequently used site near the C345C domain. In contrast, α_Mβ₂ uses its αI domain to bind iC3b at the thioester domain and simultaneously interacts through a region near the α_M β-propeller and β₂ βI domain with a region of the C3c moiety near the C345C domain. Remarkably, there is no overlap between the primary binding site of α_Xβ₂ and the binding site of α_Mβ₂ on iC3b. Distinctive binding sites on iC3b by integrins α_Xβ₂ and α_Mβ₂ may be biologically beneficial for leukocytes to more efficiently capture opsonized pathogens and to avoid subversion by pathogen factors. [ABSTRACT FROM AUTHOR]