Structural insight on the recognition of surface-bound opsonins by the integrin i domain of complement receptor 3

Complement receptors (CRs), expressed notably on myeloid and lymphoid cells, play an essential function in the elimination of complement-opsonized pathogens and apoptotic/necrotic cells. In addition, these receptors are crucial for the cross-talk between the innate andadaptive branches of theimmune system.CR3 (alsoknown as Mac-1, integrin ?Mβ2, or CD11b/CD18) is expressed on all macrophages and recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. We demonstrate that the C3d moiety of iC3b harbors the binding site for the CR3 ?I domain, and our structure of theC3d:?I domain complex rationalizes the CR3 selectivity for iC3b. Based on extensive structural analysis, we suggest that the choice between a ligand glutamate or aspartate for coordination of a receptor metal ion-dependent adhesion site-bound metal ion is governed by the secondary structure of the ligand. Comparison of our structure tothe CR2:C3dcomplexandtheinvitroformationof a stable CR3:C3d: CR2 complex suggests a molecular mechanism for the hand-over of CR3-bound immune complexes frommacrophages to CR2-presenting cells in lymph nodes.