Characterization of β₂-Glycoprotein I Binding to Phospholipid Membranes

Summary

The plasma protein β₂-glycoprotein I (β₂-GPI) is a major target of autoantibodies in patients with the antiphospholipid syndrome. To understand the physiological function of β₂-GPI and its potential role in the pathophysiology of the antiphospholipid syndrome, the binding of β₂-GPI to phospholipid membranes was characterized. The interaction of β₂-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 μM 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 β₂-GPI binding to membranes with physiological anionic phospholipid content is relatively weak in comparison to plasma coagulation proteins, suggesting that β₂-GPI does not function as a physiological anticoagulant based on its phospholipid-binding properties.

• References

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