Y. Hagihara et al., ROLE OF THE N-TERMINAL AND C-TERMINAL DOMAINS OF BOVINE BETA(2)-GLYCOPROTEIN-I IN ITS INTERACTION WITH CARDIOLIPIN, Journal of Biochemistry, 118(1), 1995, pp. 129-136
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 exami
ned the interactions of various forms of bovine beta(2)-GPI, such as i
ts intact form, desialylated form (Asialo-beta 2-GPI), N-terminal doma
in (Domain I), and modified forms of beta(2)-GPI and Asialo-beta(2)-GP
I 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 liposom
e membranes containing cardiolipin, phosphatidylglycerol, phosphatidyl
serine, phosphatidic acid, or phosphatidylinositol, but not phosphatid
ylcholine alone. The number of phospholipids involved in the binding s
eemed 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 Asi
alo-beta(2)-GPI bound to liposome membranes containing negatively char
ged 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 cardiolipi
n were both lower than those of their intact forms but similar to that
of Domain I. The pH dependencies at low and high ionic strengths and
the ionic strength dependency at neutral pH of the binding of beta(2)-
GPI to liposome membranes containing cardiolipin were similar to those
of Asialo-beta(2)-GPI, but the pH and ionic strength dependencies of
the two species were different from those of their nicked forms, the l
atter being similar to those of Domain I. These results suggest that t
he N-terminal as well as C-terminal domains have an important role in
the interaction of beta(2)-GPI with cardiolipin, and that the three re
sidual domains containing sialic acid have no significant effect on th
e interaction.