title: Structure and function of beta 2-glycoprotein I: with special reference to the interaction with phospholipid.
abstract: beta 2-Glycoprotein I (beta 2-GPI) is a cofactor in the recognition of a phospholipid antigen, cardiolipin, by anticardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examined the interaction 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 the modified forms of beta 2-GPI and Asialo beta 2-GPI with nicks in their C-terminal domains (domain 5), with phospholipid liposomes under different conditions of pH and ionic strength. We found that at neutral pH and low ionic strength beta 2-GPI bound to liposome membranes containing cardiolipin with a dissociation constant (Kd) of 10(-8) M. Phosphatidylglycerol, phosphatidylserine, phosphatidic acid or phosphatidylinositol bound to beta 2-GPI, but phosphatidylcholine did not. We also found that domain I and Asialo beta 2-GPI bound to cardiolipin with Kd values of 10(-6) and 10(-8) M, respectively. At neutral pH and both low and high ionic strengths, the affinities of nicked forms of beta 2-GPI and Asialo beta 2-GPI for cardiolipin were lower than those of intact forms but similar to that of domain 1.
authors.affiliation: Faculty of Science, University of Osaka, Toyonaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hagihara
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002417:Cattle; D006023:Glycoproteins / Q000097:blood* / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D009439:Neuraminidase / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D053482:beta 2-Glycoprotein I
chemical_list: D000596:Amino Acids; D006023:Glycoproteins; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D053482:beta 2-Glycoprotein I; D009439:Neuraminidase