Characterization of binding of human beta 2-glycoprotein I to cardiolipin.
beta 2-Glycoprotein I-cardiolipin complexes are reported to be a target antigen for the binding of a subset of anti-phospholipid antibodies. The characteristics of binding of beta 2-glycoprotein I to cardiolipin are reported in this paper. Binding at neutral pH is specific, saturable, dependent on ionic strength and independent of bivalent cation. Binding at low pH is qualitatively different from that at neutral pH, and is not dependent on ionic strength. Denaturation of beta 2-glycoprotein I by heat inactivation and reduction/alkylation indicates that beta 2-glycoprotein I-cardiolipin interaction does not require the native three-dimensional structure of beta 2-glycoprotein I, implying that a linear sequence motif may be responsible. Modification of amino acid residues by KCNO treatment completely destroys binding capacity, indicating crucial involvement of lysine residues in binding of beta 2-glycoprotein I to cardiolipin. Complement factor H, which has some similar highly charged linear sequence motifs to beta 2-glycoprotein I and is composed of the same type of protein module, was found to bind to cardiolipin and inhibit the binding of beta 2-glycoprotein I to cardiolipin. Three different lysine-rich segments of the fifth domain of beta 2-glycoprotein I may be involved in binding to cardiolipin.
Kertesz
Z
Z
Department of Biochemistry, University of Oxford, U.K.
Yu
B B
BB
Steinkasserer
A
A
Haupt
H
H
Benham
A
A
Sim
R B
RB
D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism*; D002413:Cations, Divalent; D017242:Complement Factor H / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D011485:Protein Binding; D011489:Protein Denaturation; D053482:beta 2-Glycoprotein I
D001053:Apolipoproteins; D001798:Blood Proteins; C493495:CFH protein, human; D002308:Cardiolipins; D002413:Cations, Divalent; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D053482:beta 2-Glycoprotein I; D017242:Complement Factor H