Structural insight on the recognition of surface-bound opsonins by the integrin αI-domain of complement receptor 3
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1
Aarhus University, Department of Molecular Biology and Genetics, Denmark
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2
Aarhus University, Department of Biomedicine, Denmark
Complement is the first line of defense against invading pathogens and bridges the innate and the adaptive immunity. Complement activation leads to proteolysis of the central complement component, C3, yielding an anaphylatoxin C3a and an opsonin C3b. The latter becomes covalently bound to the target surface via its reactive thioester. C3b is further processed into iC3b and C3dg by factors I and H and finally to C3d by other plasma proteases. These fragments are ligands for complement receptors expressed on immune cells. Amongst these, integrin receptors CR3 (CD11b/CD18, αMβ2, Mac-1) and CR4 (CD11c/CD18, αXβ2) are essential for the recognition and phagocytosis of immune complexes. Until now, a systematic comparison of the binding selectivity amongst C3 fragments for these receptors has been lacking. Furthermore the CR3 binding-site on the C3 molecule has not been identified so far.
By using cell-adhesion and SPR assays, we have identified the minimal binding domain of C3 for CR3. Surprisingly, these results reveal a difference in selectivity towards C3 fragments for CR3 and CR4, since CR3 preferentially binds to C3d. Furthermore, we report the crystal structure of the CR3 I-domain in complex with C3d at 2.8 Å resolution. This structure provides the first atomic model for CR3 binding to iC3b, C3dg or C3d and explains the lack of binding to C3b. In addition, our structure suggests a simultaneous binding of CR3 and another receptor, CR2, to C3 fragments, which might be important for trafficking of opsonized antigen in lymph nodes between B-cells and follicular dendritic cells.
Keywords:
Immunity,
innate immunity,
Innate immune system,
Complement System Proteins,
Complement C3,
Integrins,
Structure,
Structural Biology,
X-ray crystallography
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Bajic
G,
Yatime
L,
Vorup-Jensen
T and
Andersen
GR
(2013). Structural insight on the recognition of surface-bound opsonins by the integrin αI-domain of complement receptor 3.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01020
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Received:
29 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Gregers R Andersen, Aarhus University, Department of Molecular Biology and Genetics, Aarhus, 8000, Denmark, gra@mbg.au.dk