Molecular definition of human beta 2-glycoprotein I (beta 2-GPI) by cDNA cloning and inter-species differences of beta 2-GPI in alternation of anticardiolipin binding.
Human beta 2-glycoprotein I (beta 2-GPI) is involved in cardiolipin (CL) binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). We examined the inter-species differences of beta 2-GPI in alternation of CL binding of aCL. beta 2-GPI preparations were obtained from human, bovine, and rat sera by sequential CL--polyacrylamide affinity, DEAE--cellulose, and anti-human IgG-conjugated Sepharose CL-4B column chromatography, and they had apparent molecular weights of 50, 53, and 55 kDa respectively. Human beta 2-GPI not only enhanced CL binding by aCL in SLE but also depressed it by those in syphilis. Either bovine and rat beta 2-GPI exerted no or quite small inhibition of the binding of syphilitic aCL compared with human beta 2-GPI whereas all three species of beta 2-GPI generated binding of aCL in SLE to a similar degree. Further, a complete cDNA clone, p beta 2-GPI, was isolated from a human hepatoma cell line, HepG2, and its nucleotide sequence was analyzed. The sequences of bovine and rat counterpart molecules (beta 2-GPI) are highly homologous to that of the deduced sequence, and their corresponding regions are 84.0 and 82.5% identical to the complete domain and to the amino acid sequence 53-326 of human beta 2-GPI respectively. One of major differences appears at position 154 in human beta 2-GPI, and might be associated with the inhibitory effect on the binding of syphilitic aCL. The sequencing analysis of these beta 2-GPI proteins might provide leads to functional sites of domains which would be associated with such serological phenomena.
Matsuura
E
E
Immunology Laboratory, Yamasa Shoyu Co., Ltd, Chiba, Japan.
Igarashi
M
M
Igarashi
Y
Y
Nagae
H
H
Ichikawa
K
K
Yasuda
T
T
Koike
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002308:Cardiolipins / Q000276:immunology; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D016415:Sequence Alignment; D053482:beta 2-Glycoprotein I
D002308:Cardiolipins; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I; D004247:DNA