Recombinant hepatitis B surface antigen and anionic phospholipids share a binding region in the fifth domain of β2-glycoprotein I (apolipoprotein H)

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1782

Article

Mehdi, Haider¹  Naqvi, Asma¹  Kamboh, M. Ilyas¹ 

[1] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA

关键词: hepatitis B surface antigen;    beta 2-glycoprotein I;    apolipoprotein H;    anionic phospholipid;   

DOI  :  10.1016/j.bbadis.2008.01.001

来源: Elsevier

【 摘 要 】

Human beta(2)-glycoprotein I (beta(2)GPI) binds to recombinant hepatitis B surface antigen (rHBsAg), but the location of the binding domain on beta(2)GPI is unknown. It has been suggested that the lipid rather than the protein moiety of rHBsAg binds to beta(2)GPI. Since beta(2)GPI binds to anionic phospholipids (PL) through its lipid-binding region in the fifth domain of 1 beta(2)GPI, we predicted that this lipid-binding region may also be involved in binding rHBsAg. In this study, we examined rHBsAg binding to two naturally occurring mutants of beta(2)GPI, Cys306GIy and Trp316Ser, or evolutionarily conserved hydrophobic amino acid sequence, Leu313-Ala314-Phe315 in the fifth domain Of beta(2)GPI. The two naturally occurring mutations and two mutagenized amino acids, Leu313GIy or Phe315Ser, disrupted the binding of recombinant beta(2)GPI (r beta(2)GPI) to both rHBsAg and cardiolipin (CL), an anionic PL. These results suggest that rHBsAg and CL share the same region in the fifth domain of beta(2)GPI. Credence to this conclusion was further provided by competitive ELISA, where CL-bound r beta(2)GPI was incubated with increasing amounts of rHBsAg. As expected, pre-incubation of r beta(2)GPI with CL precluded binding to rHBsAg, indicating that CL and rHBsAg bind to the same region on beta(2)GPI. Our data provide evidence that the lipid (PL) rather than the protein moiety of rHBsAg binds to beta(2)GPI and that this binding region is located in the fifth domain of beta(2)GPI, which also binds to anionic PL. (C) 2008 Elsevier B.V. All rights reserved.

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