STRUCTURE AND FUNCTION OF BETA(2)-GLYCOPROTEIN-I - WITH SPECIAL REFERENCE TO THE INTERACTION WITH PHOSPHOLIPID

beta(2)-Glycoprotein I (beta(2)-GPI) is a cofactor in the recognition of a phospholipid antigen, cardiolipin, by anticardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examin ed the interaction of various forms of bovine beta(2)-GPI, such as its intact form, desialylated form (Asialo beta(2)-GPI), N-terminal domai n (domain 1) and the modified forms of beta(2)-GPI and Asialo beta(2)- GPI with nicks in their C-terminal domains (domain 5), with phospholip id liposomes under different conditions of pH and ionic strength. We f ound that at neutral pH and low ionic strength beta(2)-GPI bound to li posome membranes containing cardiolipin with a dissociation constant ( Kd) of 10(-8) M. Phosphatidylglycerol, phosphatidylserine, phosphatidi c acid or phosphatidylinositol bound to beta(2)-GPI, but phosphatidylc holine did not. We also found that domain 1 and Asialo beta(2)-GPI bou nd to cardiolipin with Kd values of 10(-6) and 10(-8) M, respectively, At neutral pH and both low and high ionic strengths, the affinities o f nicked forms of beta(2)-GPI and Asialo beta(2)-GPI for cardiolipin w ere lower than those of intact forms but similar to that of domain 1.