Molecular basis for complement recognition by integrin α Xβ 2

Abstract

Integrin α Xβ 2 functions as complement receptor for iC3b and mediates recognition and phagocytosis of pathogens. We used negative-stain EM to examine the α Xβ 2 interaction with iC3b. EM class averages of α Xβ 2 in complex with iC3b define the binding sites on both the integrin and iC3b. iC3b contains C3c and thioester domain moieties linked by a long flexible linker. The binding site is on the key ring of the C3c moiety, at the interface between the MG3 and MG4 domains. Similar complexes are seen between α Xβ 2 and the C3c fragment. α Xβ 2 binds through the α X αI domain, on the face known to bear the metal ion-dependent adhesion site, at the opposite end of the αI domain from its site of insertion in the β-propeller domain.