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 and adaptive branches of the immune system. CR3 (also known as Mac-1, integrin αMβ2, 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 αI domain, and our structure of the C3d:αI 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 to the CR2:C3d complex and the in vitro formation of a stable CR3:C3d:CR2 complex suggests a molecular mechanism for the hand-over of CR3-bound immune complexes from macrophages to CR2-presenting cells in lymph nodes.
Departments of Molecular Biology and Genetics and Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
Goran
G
Bajic
Laure
L
Yatime
Robert B
RB
Sim
Thomas
T
Vorup-Jensen
Gregers R
GR
Andersen
D003179:Complement C3b / Q000378:metabolism*; D019295:Computational Biology; D004926:Escherichia coli; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000737:chemistry* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008958:Models, Molecular; D009895:Opsonin Proteins / Q000737:chemistry* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011487:Protein Conformation
D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D003179:Complement C3b
innate immunity; integrin receptor; phagocytosis; structural biology