Characterization of β2-glycoprotein I binding to phospholipid membranes

The plasma protein beta(2)-glycoprotein I (beta(2)-GPI) is a major target of autoantibodies in patients with the antiphospholipid syndrome. To understand the physiological function of beta(2)-GPI and its potential role in the pathophysiology of the antiphospholipid syndrome, the binding of beta(2)-GPI to phospholipid membranes was characterized. The interaction of beta(2)-GPI with unilamellar vesicles containing varying amounts of acidic phospholipids with phosphatidylcholine (PC) was measured at equilibrium via relative light scattering. Analysis of binding isotherms gave apparent K-d values ranging from approximately 5.0 to 0.5 mu M over a range of 5-20 mol % anionic phospholipid. Inhibition of binding by increasing ionic strength and Ca2+ ions suggests that binding is primarily electrostatic. These data indicate that beta(2)-GPI binding to membranes with physiological anionic phospholipid content is relatively weak in comparison to plasma coagulation proteins, suggesting that beta(2)-GPI does not function as a physiological anticoagulant based on its phospholipid-binding properties.