Structure and Function of β2-Glycoprotein I: With Special Reference to the Interaction with Phospholipid

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Abstract
β2-Glycoprotein I (β2-GPI) is a cofactor in the recognition of a phospholipid antigen, cardiolipin, by anticardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examined the interaction of various forms of bovine β2-GPI, such as its intact form, desialylated form (Asialo β2-GPI), N-terminal domain (domain 1) and the modified forms of β2-GPI and Asialo β2-GPI with nicks in their C-terminal domains (domain 5), with phospholipid liposomes under different conditions of pH and ionic strength. We found that at neutral pH and low ionic strength β2-GPI bound to liposome membranes containing cardiolipin with a dissociation constant (Kd) of 10−8 M. Phosphatidylglycerol, phosphatidylserine, phosphatidic acid or phosphatidylinositol bound to β2-GPI, but phosphatidylcholine did not. We also found that domain 1 and Asialo β2-GPI bound 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 of nicked forms of β2-GPI and Asialo β2-GPI for cardiolipin were lower than those of intact forms but similar to that of domain 1.