Abstract
Alpha-2-macroglobulin (α2-MG) is a high-molecular weight glycoprotein with a broad spectrum of regulatory functions. As was shown earlier, covalent binding of α2-MG to proteases results in its conformational transformation, which allows α2-MG to transport additionally certain types of cytokines, attached via non-covalent interactions. Our results have shown that the spectrum of proteins exhibiting additional binding to the transformed α2-MG is rather broad and includes three classes of immunoglobulins, albumin, both types of lipoproteins, plasmin, some cytokines, and even pregnancy-associated alpha-2-glycoprotein (a structural homologue of α2-MG). The main ligands are albumin, IgG, plasmin, and to a lesser extent, lipoproteins. Interaction of native α2-MG with both acidic and weakly alkaline proteases results in neutralization net charge of the formed complex at pH, characteristic for internal media of the body. Addition of LRP (the low density lipoprotein related protein) increased the amount of electrically neutral complexes at pH 7.4. We believe that the transformed α2-MG (possibly in the complex with other effector proteins) employs similar mechanism for quick adsorption on the cell surface; after binding to LRP and repeated neutralization of the net charge at physiological pH, it “falls” through into the cell membrane and realize its regulatory functions.
Similar content being viewed by others
References
Armstrong, P.B., and Quigley, J.P., Dev. Comp. Immunol., 1999, vol. 23, pp. 375–390.
Zorin, N.A., and Zorina, V.N., Zh. Mikrobiol. Epidemiol. Immunol., 2004, no. 3, pp. 105–112.
Tayade, C., Esadeg, S., Fang. Y., and Croy, B.A., Mol. Cell. Endocrinol., 2005, vol. 245, pp. 60–66.
Zorin, N.A., Zorina, V.N., and Zorina, R.M., Zh. Evol. Biokhim. Fiziol., 2006, vol. 42, pp. 92–95.
Petersen, C.M., Danish Med. Bull., 1993, vol. 40, pp. 409–446.
Birkenmeier, G., Mod. Asp. Immunol., 2001, vol. 2, pp. 32–36.
Zorin, N.A., Zorina, V.N., and Zorina, R.M., Biomed. Khim., 2006, vol. 52, pp. 229–238.
Chiabrando, G.A., Vides, M.A., and Sanchez, M.C., Arch. Biochem. Biophys., 2002, vol. 398, pp. 73–78.
Zorin, N.A. and Zorina, V.N., Hematol. Transfuziol., 2000, no. 5, pp. 20–21.
Zorin, N.A., Lab. Delo, 1983, no. 10, pp. 40–43.
Zorin, N.A., and Zhabin, S.G., Hematol. Transfuziol., 1992, no. 9–10, pp. 42–43.
Zorin, N.A., Zhabin, S.G., and Semenkov, N.N., Clin. Chim. Acta, 1995, vol. 239, pp. 47–55.
Webb, D.J., Roadcap, D.W., and Dhakenphalkar, A., Protein Sci., 2000, vol. 9, pp. 1986–1992.
Sand, O., Folkersen, J., Westergaard, J.C., and Sottrup-Jensen, L., J. Biol. Chem., 1985, vol. 260, pp. 15723–15735.
Burger, D., and Dayer, J.M., Autoimmun. Rev., 2002, vol. 1, pp. 111–117.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © V.N. Zorina, N.A. Zorin, O.F. Lykova, T.V. Konysheva, R.M. Zorina, 2007, published in Biomeditsinskaya Khimiya.
Rights and permissions
About this article
Cite this article
Zorina, V.N., Zorin, N.A., Lykova, O.F. et al. Alpha-2 macroglobulin ligands and mechanisms of their biotransport. Biochem. Moscow Suppl. Ser. B 1, 216–219 (2007). https://doi.org/10.1134/S1990750807030067
Received:
Issue Date:
DOI: https://doi.org/10.1134/S1990750807030067