Role of the N- and C-terminal domains of bovine beta 2-glycoprotein I in its interaction with cardiolipin.
beta 2-Glycoprotein I (beta 2-GPI) is a cofactor in the recognition of the phospholipid antigen cardiolipin by anti-cardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examined the interactions of various forms of bovine beta 2-GPI, such as its intact form, desialylated form (Asialo-beta 2-GPI), N-terminal domain (Domain I), and modified forms of beta 2-GPI and Asialo-beta 2-GPI with nicks in their C-terminal domains, with phospholipid liposomes under different conditions of pH and ionic strength. We found that at neutral pH and low ionic strength, beta 2-GPI became bound to liposome membranes containing cardiolipin, phosphatidylglycerol, phosphatidylserine, phosphatidylserine, phosphatidic acid, or phosphatidylinositol, but not phosphatidylcholine alone. The number of phospholipids involved in the binding seemed to depend on the head group structure of the negatively charged phospholipids, but the dissociation constant did not, being about 10(-8) M, except that for the interaction with phosphatidylinositol, which was one order of magnitude lower. We also found that Domain I and Asialo-beta 2-GPI bound to liposome membranes containing negatively charged phospholipids, and that in the interaction with cardiolipin, their dissociation constants were about 10(-6) and 10(-8) M, respectively. At neutral pH and both low and high ionic strengths, the affinities of the nicked forms of beta 2-GPI and Asialo-beta 2-GPI for cardiolipin were both lower than those of their intact forms but similar to that of Domain I.(ABSTRACT TRUNCATED AT 250 WORDS)
Faculty of Science, University of Osaka.
Y
Y
Hagihara
Y
Y
Goto
H
H
Kato
T
T
Yoshimura
D000818:Animals; D000838:Anions; D002308:Cardiolipins / Q000737:chemistry*; D002417:Cattle; D006023:Glycoproteins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D009994:Osmolar Concentration; D010743:Phospholipids / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D053482:beta 2-Glycoprotein I
D000838:Anions; D002308:Cardiolipins; D006023:Glycoproteins; D008081:Liposomes; D010743:Phospholipids; C097476:asialo-beta 2-glycoprotein I; D053482:beta 2-Glycoprotein I