Interaction of vitronectin with a novel human protein, gClgR

A novel protein (gClqR) which is able to bind the globular heads of complement component Clq, has recently been found on vascular and blood cells . A recombinant form of the protein was expressed in bacteria to investigate its functional and structural properties. Recombinant gClqR immobilized to microspheres was used to search for additional binding proteins unrelated to Clq. Surprisingly, in unfractionated human serum or plasma, vitronectin containing material was retained, and subsequent analysis revealed the specific binding of the ternary vitronectin-thrombin-antithrombin complex from serum to gClqR. Since the thrombin-antithrombin complex was unable to interact with gClqR, direct interaction with vitronectin was investigated in a purified system. Specific binding of heparin-binding multimeric vitronectin but not the plasma form to gClqR was demonstrated to be saturable (KD "" 50 nM) and inhabitable by heparin. While Clq binding was not affected by vitronectin, Clq itself augmented vitronectin binding to soluble gClqR appreciably. Both, Clq and vitronectin appear to interact with different parts of the receptor, since a truncated version of gClqR lacking the N-terminal 22 amino acid portion hardly interacted with the adhesive protein but bound Clq equally well. These findings establish gClqR as a novel vitronectin receptor/binding protein that may participate in the clearance of vitronectincontaining complexes during vitronectin-opsonized phagocytosis or becomes involved in the inhibition of complement-mediated cytosis.