Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1995 Aug 15;310(Pt 1):315–321. doi: 10.1042/bj3100315

Characterization of binding of human beta 2-glycoprotein I to cardiolipin.

Z Kertesz 1, B B Yu 1, A Steinkasserer 1, H Haupt 1, A Benham 1, R B Sim 1
PMCID: PMC1135890  PMID: 7646462

Abstract

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.

Full text

PDF
315

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aoyama Y., Chan Y. L., Wool I. G. The primary structure of rat beta 2-glycoprotein I. Nucleic Acids Res. 1989 Aug 11;17(15):6401–6401. doi: 10.1093/nar/17.15.6401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bendixen E., Halkier T., Magnusson S., Sottrup-Jensen L., Kristensen T. Complete primary structure of bovine beta 2-glycoprotein I: localization of the disulfide bridges. Biochemistry. 1992 Apr 14;31(14):3611–3617. doi: 10.1021/bi00129a009. [DOI] [PubMed] [Google Scholar]
  3. Day J. R., O'Hara P. J., Grant F. J., Lofton-Day C., Berkaw M. N., Werner P., Arnaud P. Molecular cloning and sequence analysis of the cDNA encoding human apolipoprotein H (beta 2-glycoprotein I). Int J Clin Lab Res. 1992;21(3):256–263. doi: 10.1007/BF02591656. [DOI] [PubMed] [Google Scholar]
  4. Fairbanks G., Steck T. L., Wallach D. F. Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry. 1971 Jun 22;10(13):2606–2617. doi: 10.1021/bi00789a030. [DOI] [PubMed] [Google Scholar]
  5. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  6. Galli M., Comfurius P., Maassen C., Hemker H. C., de Baets M. H., van Breda-Vriesman P. J., Barbui T., Zwaal R. F., Bevers E. M. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet. 1990 Jun 30;335(8705):1544–1547. doi: 10.1016/0140-6736(90)91374-j. [DOI] [PubMed] [Google Scholar]
  7. Harris N. E., Pierangeli S. What is the "true" antigen for antiphospholipid antibodies? Lancet. 1990 Dec 15;336(8729):1505–1505. doi: 10.1016/0140-6736(90)93208-7. [DOI] [PubMed] [Google Scholar]
  8. Hunt J., Krilis S. The fifth domain of beta 2-glycoprotein I contains a phospholipid binding site (Cys281-Cys288) and a region recognized by anticardiolipin antibodies. J Immunol. 1994 Jan 15;152(2):653–659. [PubMed] [Google Scholar]
  9. Kato H., Enjyoji K. Amino acid sequence and location of the disulfide bonds in bovine beta 2 glycoprotein I: the presence of five Sushi domains. Biochemistry. 1991 Dec 17;30(50):11687–11694. doi: 10.1021/bi00114a012. [DOI] [PubMed] [Google Scholar]
  10. Kristensen T., Schousboe I., Boel E., Mulvihill E. M., Hansen R. R., Møller K. B., Møller N. P., Sottrup-Jensen L. Molecular cloning and mammalian expression of human beta 2-glycoprotein I cDNA. FEBS Lett. 1991 Sep 9;289(2):183–186. doi: 10.1016/0014-5793(91)81065-g. [DOI] [PubMed] [Google Scholar]
  11. Kroll J., Larsen J. K., Loft H., Ezban M., Wallevik K., Faber M. DNA-binding proteins in Yoshida ascites tumor fluid. Biochim Biophys Acta. 1976 Jun 15;434(2):490–501. doi: 10.1016/0005-2795(76)90239-7. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Lauer S. A., Hempel U., Gries A., Frank K. H. Amino acid sequence of the region of beta 2-glycoprotein 1 (gp1) which mediates binding of autoantibodies to the cardiolipin-gp1 complex in humans. Immunology. 1993 Sep;80(1):22–28. [PMC free article] [PubMed] [Google Scholar]
  14. Lozier J., Takahashi N., Putnam F. W. Complete amino acid sequence of human plasma beta 2-glycoprotein I. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3640–3644. doi: 10.1073/pnas.81.12.3640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Matsuura E., Igarashi M., Igarashi Y., Nagae H., Ichikawa K., Yasuda T., Koike T. 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. Int Immunol. 1991 Dec;3(12):1217–1221. doi: 10.1093/intimm/3.12.1217. [DOI] [PubMed] [Google Scholar]
  16. Matsuura E., Igarashi Y., Fujimoto M., Ichikawa K., Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet. 1990 Jul 21;336(8708):177–178. doi: 10.1016/0140-6736(90)91697-9. [DOI] [PubMed] [Google Scholar]
  17. McNeil H. P., Simpson R. J., Chesterman C. N., Krilis S. A. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A. 1990 Jun;87(11):4120–4124. doi: 10.1073/pnas.87.11.4120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Medved L. V., Busby T. F., Ingham K. C. Calorimetric investigation of the domain structure of human complement Cl-s: reversible unfolding of the short consensus repeat units. Biochemistry. 1989 Jun 27;28(13):5408–5414. doi: 10.1021/bi00439a014. [DOI] [PubMed] [Google Scholar]
  19. Nimpf J., Bevers E. M., Bomans P. H., Till U., Wurm H., Kostner G. M., Zwaal R. F. Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I. Biochim Biophys Acta. 1986 Oct 29;884(1):142–149. doi: 10.1016/0304-4165(86)90237-0. [DOI] [PubMed] [Google Scholar]
  20. Nimpf J., Wurm H., Kostner G. M. Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation. Atherosclerosis. 1987 Feb;63(2-3):109–114. doi: 10.1016/0021-9150(87)90110-9. [DOI] [PubMed] [Google Scholar]
  21. Nimpf J., Wurm H., Kostner G. M. Interaction of beta 2-glycoprotein-I with human blood platelets: influence upon the ADP-induced aggregation. Thromb Haemost. 1985 Aug 30;54(2):397–401. [PubMed] [Google Scholar]
  22. Nonaka M., Matsuda Y., Shiroishi T., Moriwaki K., Nonaka M., Natsuume-Sakai S. Molecular cloning of mouse beta 2-glycoprotein I and mapping of the gene to chromosome 11. Genomics. 1992 Aug;13(4):1082–1087. doi: 10.1016/0888-7543(92)90022-k. [DOI] [PubMed] [Google Scholar]
  23. Polz E., Kostner G. M. The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions. FEBS Lett. 1979 Jun 1;102(1):183–186. doi: 10.1016/0014-5793(79)80955-2. [DOI] [PubMed] [Google Scholar]
  24. Polz E., Wurm H., Kostner G. M. Investigations on beta 2-glycoprotein-I in the rat: isolation from serum and demonstration in lipoprotein density fractions. Int J Biochem. 1980;11(3-4):265–270. doi: 10.1016/0020-711x(80)90229-3. [DOI] [PubMed] [Google Scholar]
  25. Reid K. B., Day A. J. Structure-function relationships of the complement components. Immunol Today. 1989 Jun;10(6):177–180. doi: 10.1016/0167-5699(89)90317-4. [DOI] [PubMed] [Google Scholar]
  26. Ripoche J., Day A. J., Harris T. J., Sim R. B. The complete amino acid sequence of human complement factor H. Biochem J. 1988 Jan 15;249(2):593–602. doi: 10.1042/bj2490593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schousboe I. Binding of beta 2-glycoprotein I to platelets: effect of adenylate cyclase activity. Thromb Res. 1980 Jul 1;19(1-2):225–237. doi: 10.1016/0049-3848(80)90421-1. [DOI] [PubMed] [Google Scholar]
  28. Schousboe I. Characterization of the interaction between beta 2-glycoprotein I and mitochondria, platelets, liposomes and bile acids. Int J Biochem. 1983;15(12):1393–1401. doi: 10.1016/0020-711x(83)90070-8. [DOI] [PubMed] [Google Scholar]
  29. Schousboe I. Purification, characterization and identification of an agglutinin in human serum. Biochim Biophys Acta. 1979 Aug 28;579(2):396–408. doi: 10.1016/0005-2795(79)90067-9. [DOI] [PubMed] [Google Scholar]
  30. Sellar G. C., Keane J., Mehdi H., Peeples M. E., Browne N., Whitehead A. S. Characterization and acute phase modulation of canine apolipoprotein H (beta 2-glycoprotein I). Biochem Biophys Res Commun. 1993 Mar 31;191(3):1288–1293. doi: 10.1006/bbrc.1993.1357. [DOI] [PubMed] [Google Scholar]
  31. Sim R. B., DiScipio R. G. Purification and structural studies on the complement-system control protein beta 1H (Factor H). Biochem J. 1982 Aug 1;205(2):285–293. doi: 10.1042/bj2050285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Steinkasserer A., Barlow P. N., Willis A. C., Kertesz Z., Campbell I. D., Sim R. B., Norman D. G. Activity, disulphide mapping and structural modelling of the fifth domain of human beta 2-glycoprotein I. FEBS Lett. 1992 Nov 23;313(2):193–197. doi: 10.1016/0014-5793(92)81442-o. [DOI] [PubMed] [Google Scholar]
  33. Steinkasserer A., Estaller C., Weiss E. H., Sim R. B., Day A. J. Complete nucleotide and deduced amino acid sequence of human beta 2-glycoprotein I. Biochem J. 1991 Jul 15;277(Pt 2):387–391. doi: 10.1042/bj2770387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Williams S. C., Sim R. B. Dye-ligand affinity purification of human complement factor B and beta 2 glycoprotein I. J Immunol Methods. 1993 Jan 4;157(1-2):25–30. doi: 10.1016/0022-1759(93)90066-g. [DOI] [PubMed] [Google Scholar]
  35. Wurm H. beta 2-Glycoprotein-I (apolipoprotein H) interactions with phospholipid vesicles. Int J Biochem. 1984;16(5):511–515. doi: 10.1016/0020-711x(84)90168-x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES