CHARACTERIZATION OF BINDING OF HUMAN BETA(2)-GLYCOPROTEIN-I TO CARDIOLIPIN

beta(2)-Glycoprotein I-cardiolipin complexes are reported to be a targ et antigen for the binding of a subset of anti-phospholipid antibodies . The characteristics of binding of beta(2)-glycoprotein I to cardioli pin are reported in this paper. Binding at neutral pH is specific, sat urable, dependent on ionic strength and independent of bivalent cation . Binding at low pH is qualitatively different from that at neutral pH , and is not dependent on ionic strength. Denaturation of beta(2)-glyc oprotein I by heat inactivation and reduction/alkylation indicates tha t beta(2)-glycoprotein I-cardiolipin . interaction does not require-th e native three-dimensional structure of beta(2)-glycoprotein I, implyi ng that a linear sequence motif may be responsible. Modification of am ino acid residues by KCNO treatment completely destroys binding capaci ty, indicating crucial involvement of lysine residues in binding of be ta(2)-glycoprotein I to cardiolipin. Complement factor H, which has so me similar highly charged linear sequence motifs to beta(2)-glycoprote in I and is composed of the same type of protein module, was found to bind to cardiolipin and inhibit the binding of beta(2)-glycoprotein I to cardiolipin. Three different lysine-rich segments of the fifth doma in of beta(2)-glycoprotein I may be involved in binding to cardiolipin .