Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1995 Aug 1;309(Pt 3):899–904. doi: 10.1042/bj3090899

The binding of animal low-density lipoproteins to human apolipoprotein(a).

V N Trieu 1, W J McConathy 1
PMCID: PMC1135716  PMID: 7639708

Abstract

Lipoprotein(a) [Lp(a)] is a risk factor for coronary artery disease. It is composed of lipids and apolipoprotein(a) [apo(a)] linked to apolipoprotein B (apoB) by a disulphide bond between Cys-4057 of apo(a)'s kringle 36 and possibly Cys-3734 of apoB. We call this the covalent apo(a): apoB-Lp interaction, to distinguish it from the non-covalent apo(a)/Lp(a): apoB-Lp interaction, which is probably mediated by apo(a)'s kringle 33 and residues 3304-3317 of apoB. The non-covalent interaction could be the initial interaction which brings apo(a) and apoB together prior to covalent linkage and Lp(a) formation. The non-covalent apo(a)/Lp(a)-binding site on apoB is evolutionarily more ancient than the covalent apo(a)-binding site on apoB. Both human and non-human low-density lipoproteins (LDLs) bind non-covalently to human apo(a)/Lp(a); however, only rabbit and human LDLs bind covalently to human apo(a). The non-covalent interaction between mouse LDL and human apo(a)/Lp(a) has a Kd of (1.7 +/- 1.33) x 10(-7) M (n = 3). This explains the co-localization of human apo(a) and mouse apoB in the atherosclerotic lesions of human apo(a) transgenic mice and supports our hypothesis that the non-covalent interaction is a contributing factor to apo(a) atherogenicity.

Full text

PDF
899

Images in this article

901Figure 2
on p.901
901Figure 3
on p.901
902Figure 4
on p.902
902Figure 5
on p.902
902Figure 6
on p.902

Selected References

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

  1. Armstrong V. W., Cremer P., Eberle E., Manke A., Schulze F., Wieland H., Kreuzer H., Seidel D. The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels. Atherosclerosis. 1986 Dec;62(3):249–257. doi: 10.1016/0021-9150(86)90099-7. [DOI] [PubMed] [Google Scholar]
  2. Brunner C., Kraft H. G., Utermann G., Müller H. J. Cys4057 of apolipoprotein(a) is essential for lipoprotein(a) assembly. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11643–11647. doi: 10.1073/pnas.90.24.11643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chapman M. J. Comparative analysis of mammalian plasma lipoproteins. Methods Enzymol. 1986;128:70–143. doi: 10.1016/0076-6879(86)28063-5. [DOI] [PubMed] [Google Scholar]
  4. Chiesa G., Hobbs H. H., Koschinsky M. L., Lawn R. M., Maika S. D., Hammer R. E. Reconstitution of lipoprotein(a) by infusion of human low density lipoprotein into transgenic mice expressing human apolipoprotein(a). J Biol Chem. 1992 Dec 5;267(34):24369–24374. [PubMed] [Google Scholar]
  5. Coleman R. D., Kim T. W., Gotto A. M., Jr, Yang C. Y. Determination of cysteine on low-density lipoproteins using the fluorescent probe, 5-iodoacetamidofluoresceine. Biochim Biophys Acta. 1990 Jan 19;1037(1):129–132. doi: 10.1016/0167-4838(90)90111-r. [DOI] [PubMed] [Google Scholar]
  6. Dahlen G. H., Guyton J. R., Attar M., Farmer J. A., Kautz J. A., Gotto A. M., Jr Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation. 1986 Oct;74(4):758–765. doi: 10.1161/01.cir.74.4.758. [DOI] [PubMed] [Google Scholar]
  7. Durrington P. N., Ishola M., Hunt L., Arrol S., Bhatnagar D. Apolipoproteins (a), AI, and B and parental history in men with early onset ischaemic heart disease. Lancet. 1988 May 14;1(8594):1070–1073. doi: 10.1016/s0140-6736(88)91895-8. [DOI] [PubMed] [Google Scholar]
  8. Fless G. M., Snyder M. L., Furbee J. W., Jr, Garcia-Hedo M. T., Mora R. Subunit composition of lipoprotein(a) protein. Biochemistry. 1994 Nov 15;33(45):13492–13501. doi: 10.1021/bi00249a038. [DOI] [PubMed] [Google Scholar]
  9. Fless G. M., ZumMallen M. E., Scanu A. M. Physicochemical properties of apolipoprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein (a). J Biol Chem. 1986 Jul 5;261(19):8712–8718. [PubMed] [Google Scholar]
  10. Frank S., Durovic S., Kostner G. M. Structural requirements of apo-a for the lipoprotein-a assembly. Biochem J. 1994 Nov 15;304(Pt 1):27–30. doi: 10.1042/bj3040027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frank S., Krasznai K., Durovic S., Lobentanz E. M., Dieplinger H., Wagner E., Zatloukal K., Cotten M., Utermann G., Kostner G. M. High-level expression of various apolipoprotein(a) isoforms by "transferrinfection": the role of kringle IV sequences in the extracellular association with low-density lipoprotein. Biochemistry. 1994 Oct 11;33(40):12329–12339. doi: 10.1021/bi00206a041. [DOI] [PubMed] [Google Scholar]
  12. Guevara J., Jr, Spurlino J., Jan A. Y., Yang C. Y., Tulinsky A., Prasad B. V., Gaubatz J. W., Morrisett J. D. Proposed mechanisms for binding of apo[a] kringle type 9 to apo B-100 in human lipoprotein[a]. Biophys J. 1993 Mar;64(3):686–700. doi: 10.1016/S0006-3495(93)81428-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hermier D., Forgez P., Chapman M. J. A density gradient study of the lipoprotein and apolipoprotein distribution in the chicken, Gallus domesticus. Biochim Biophys Acta. 1985 Aug 22;836(1):105–118. doi: 10.1016/0005-2760(85)90226-7. [DOI] [PubMed] [Google Scholar]
  14. Huby T., Doucet C., Dieplinger H., Chapman J., Thillet J. Structural domains of apolipoprotein(a) and its interaction with apolipoprotein B-100 in the lipoprotein(a) particle. Biochemistry. 1994 Mar 22;33(11):3335–3341. doi: 10.1021/bi00177a026. [DOI] [PubMed] [Google Scholar]
  15. Johansen T. E., Schøller M. S., Tolstoy S., Schwartz T. W. Biosynthesis of peptide precursors and protease inhibitors using new constitutive and inducible eukaryotic expression vectors. FEBS Lett. 1990 Jul 16;267(2):289–294. doi: 10.1016/0014-5793(90)80947-h. [DOI] [PubMed] [Google Scholar]
  16. Koschinsky M. L., Côté G. P., Gabel B., van der Hoek Y. Y. Identification of the cysteine residue in apolipoprotein(a) that mediates extracellular coupling with apolipoprotein B-100. J Biol Chem. 1993 Sep 15;268(26):19819–19825. [PubMed] [Google Scholar]
  17. Koschinsky M. L., Tomlinson J. E., Zioncheck T. F., Schwartz K., Eaton D. L., Lawn R. M. Apolipoprotein(a): expression and characterization of a recombinant form of the protein in mammalian cells. Biochemistry. 1991 May 21;30(20):5044–5051. doi: 10.1021/bi00234a029. [DOI] [PubMed] [Google Scholar]
  18. Law A., Scott J. A cross-species comparison of the apolipoprotein B domain that binds to the LDL receptor. J Lipid Res. 1990 Jun;31(6):1109–1120. [PubMed] [Google Scholar]
  19. Lawn R. M., Wade D. P., Hammer R. E., Chiesa G., Verstuyft J. G., Rubin E. M. Atherogenesis in transgenic mice expressing human apolipoprotein(a) Nature. 1992 Dec 17;360(6405):670–672. doi: 10.1038/360670a0. [DOI] [PubMed] [Google Scholar]
  20. Mandel R., Ryser H. J., Ghani F., Wu M., Peak D. Inhibition of a reductive function of the plasma membrane by bacitracin and antibodies against protein disulfide-isomerase. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4112–4116. doi: 10.1073/pnas.90.9.4112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McLean J. W., Tomlinson J. E., Kuang W. J., Eaton D. L., Chen E. Y., Fless G. M., Scanu A. M., Lawn R. M. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987 Nov 12;330(6144):132–137. doi: 10.1038/330132a0. [DOI] [PubMed] [Google Scholar]
  22. Phillips M. L., Lembertas A. V., Schumaker V. N., Lawn R. M., Shire S. J., Zioncheck T. F. Physical properties of recombinant apolipoprotein(a) and its association with LDL to form an LP(a)-like complex. Biochemistry. 1993 Apr 13;32(14):3722–3728. doi: 10.1021/bi00065a026. [DOI] [PubMed] [Google Scholar]
  23. Purtell C., Maeda N., Ebert D. L., Kaiser M., Lund-Katz S., Sturley S. L., Kodoyianni V., Grunwald K., Nevin D. N., Aiello R. J. Nucleotide sequence encoding the carboxyl-terminal half of apolipoprotein B from spontaneously hypercholesterolemic pigs. J Lipid Res. 1993 Aug;34(8):1323–1335. [PubMed] [Google Scholar]
  24. Rath M., Niendorf A., Reblin T., Dietel M., Krebber H. J., Beisiegel U. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis. 1989 Sep-Oct;9(5):579–592. doi: 10.1161/01.atv.9.5.579. [DOI] [PubMed] [Google Scholar]
  25. Trieu V. N., McConathy W. J. Lipoprotein(a) binding to other apolipoprotein B containing lipoproteins. Biochemistry. 1990 Jun 26;29(25):5919–5924. doi: 10.1021/bi00477a006. [DOI] [PubMed] [Google Scholar]
  26. Trieu V. N., Olsson U., McConathy W. J. The apolipoprotein B3304-3317 peptide as an inhibitor of the lipoprotein (a):apolipoprotein B-containing lipoprotein interaction. Biochem J. 1995 Apr 1;307(Pt 1):17–22. doi: 10.1042/bj3070017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. White A. L., Rainwater D. L., Lanford R. E. Intracellular maturation of apolipoprotein[a] and assembly of lipoprotein[a] in primary baboon hepatocytes. J Lipid Res. 1993 Mar;34(3):509–517. [PubMed] [Google Scholar]
  28. Ye S. Q., Trieu V. N., Stiers D. L., McConathy W. J. Interactions of low density lipoprotein2 and other apolipoprotein B-containing lipoproteins with lipoprotein(a). J Biol Chem. 1988 May 5;263(13):6337–6343. [PubMed] [Google Scholar]
  29. van der Hoek Y. Y., Kastelein J. J., Koschinsky M. L. Analysis of structure--function relationships in human apolipoprotein(a). Can J Physiol Pharmacol. 1994 Mar;72(3):304–310. doi: 10.1139/y94-046. [DOI] [PubMed] [Google Scholar]

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

RESOURCES