Summary
A key amino acid substitution specific for allotypic Gm b markers, b0, b3, b5, were determined through sequence analyses of the pFc′ fragments of IgG1 (Su) and IgG3 (Ba[Gm(g)], Bu[Gm(b1b3)], and Kam[Gm(b3st)]) myeloma proteins. The results indicate that serine at position 384 is responsible for the specificities. It is considered from crystallographic data of IgG-Fc [Deisenhoferet al. (1981)Biochemistry 20: 2361] that two residues, the serine and isoleucine specific for IgG3 subclass at position 422, cause the structural change responsible for b markers. The two residues are close to each other in the CH3 domain. The allocations of the epitopes are estimated to be on two bends (residue no. 382-392, 411-424) between the beta-strands, whose amino acid residues are present in wide contact area [Novotnyet al. (1987)Immunol. Today 8: 26).
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Amit, A.G., Mariuzza, R.A., Phillips, S.E.V. and Poljak, R.J. 1986. Three-dimensional structure of an antigen-antibody complex at 2.8 Å resolution.Science 233: 747–753.
Bidlingmeyer, B.A., Cohen, S.A. and Tarvin, T.L. 1984. Rapid analysis of amino acids using pre-column derivatization.J. Chromatogr. 336: 93–104.
Cook, C.E. and Steinberg, A.G. 1979. An amino acid substitution in the γ1 chain of human immunoglobulin G associated with the Gm(2) allotype.Mol. Immunol. 16: 555–558.
Deisenhofer, J., Colman, P.M., Otto, E. and Huber, R. 1976. Crystallographic structural studies of a human Fc fragment II. A complete model based on a Fourier map at 3.5 Å resolution.Hoppe-Seyler's Z. Physiol. Chem. 357: 1421–1434.
Edelman, G.M., Cunningham, B.A., Gall, W.E., Gottlieb, P.D., Rutishauser, U. and Waxdal, M.J. 1969. The covalent structure of an entire γG immunoglobulin molecule.Proc. Natl. Acad. Sci. U.S.A. 63: 78–85.
Frangione, B., Franklin, E.C., Fudenberg, H.H. and Koshland, M.E. 1966. Structural studies of human γG-myeloma proteins of different antigenic subgroups and genetic specificities.J. Exp. Med. 124: 715–732.
Geysen, H.M., Tainer, J.A., Rodda, S.J., Mason, T.J., Alexander, H., Getzoff, E.D. and Lerner, R.A. 1987. Chemistry of antibody binding to a protein.Science 235: 1184–1190.
Gottlieb, P.D., Cunningham, B.A., Waxdahl, M.J., Konigsberg, W.H. and Edelman, G.M. 1968. Variable regions of heavy and light polypeptide chains of the same γG-immunoglobulin molecule.Proc. Natl. Acad. Sci. U.S.A. 61: 168–175.
Grubb, R. 1970.The Genetic Markers of Human Immunoglobulins, Springer, Berlin.
Gurd, F.R.N. 1967. Carboxymethylation.Methods Enzymol. 11: 532–541.
Hopp, T.P. 1986. Protein surface analysis: methods for identifying antigenic determinants and other interaction sites.J. Immunol. 88: 1–18.
Ito, S., Yamazaki, K., Miyazaki, T. and Matsumoto, H. 1986. An amino acid substitution determining G3m(g).J. Biochem. 99: 1799–1802.
Ito, S., Suzuki, K., Matsui, K. and Matsumoto, H. 1987. Determination of bloodstain origin by high-performance liquid chromatography of the hemoglobin peptides.Act. Crim. Jpn. 53: 68–75.
Ito, S., Suzuki, K., Miyazaki, T. and Matsumoto, H. 1989. An amino acid substitution determining G1m(x) allotypic marker.Jpn. J. Legal Med. (in Japanese)43: 155–160.
Ito, S., Suzuki, K., Miyazaki, T. and Matsumoto, H. 1990. Amino acid substitutions determining G3m(g5).Exp. Clin. Immunogenet. 7: 91–100.
Lange, G.G. de, Leeuwen, A.M. van, Eede, P.H. van, Lincoln, P.J. and Engelfreit, C.P. 1988. Alloantigens on plasma proteins. Polymorphism of immunoglobulins: Gm, Am and Km typing.Adv. Haemogenet. 2: 64–71.
Matsumoto, H. and Takatsuki, K. 1968. Studies on the Gm factors of Japanese population and families.Jpn. J. Legal Med. 22: 635–642.
Matsumoto, H., Ito, S., Miyazaki, T. and Ohta, T. 1983. Structural studied of a human γ3 myeloma protein (Jir) bearing the allotypic marker Gm(st).J. Immunol. 131: 1865–1870.
Matsumoto, H., Ito, S., Miyazaki, T. and Kawai, N. 1986. Structural studies of another human IgG3 myeloma protein (Kam) carrying the allotypic markers Gm(s,t) and its alteration induced by chemical modification.Adv. Forensic Haemogenet. 1: 153–156.
Matsumoto, H. 1988. Characteristics of Mongoloid and neighboring populations based on the genetic markers of human immunoglobulins.Hum. Genet. 80: 207–218.
Matsumoto, H. 1989. Characteristics of Mongoloid populations and immunogenetics of various diseases based on the genetic markers of human immunoglobulins.Exp. Clin. Immunogenet. 6: 68–87.
Natvig, J.B. and Turner, M.W. 1971. Localization of Gm markers to different molecular regions of the Fc fragment.Clin. Exp. Immunol. 8: 685–700.
Novotny, J., Handschumacher, M. and Bruccoleri, R.E. 1987. Protein antigenicity: a static surface property.Immnol. Today. 8: 26–31.
Pink, J.R.L., Buttery, S.H., Vries, G.M. de and Milstein, C. 1970. Human immunoglobulin subclasses. Partial amino acid sequence of the constant region of a γ4 chain.Biochem. J. 117: 33–47.
Polmar, S.H. and Steinberg, A.G. 1964. Dependence of a Gm(b) antigen on the quaternary structure of human gamma globulin.Science 145: 928–929.
Press, E.M. and Hogg, N.M. 1969. Comparative study of two immunoglobulin G Fd-fragments.Nature 223: 807–810.
Press, E.M. and Hogg, N.M. 1970. The amino acid sequences of the Fd fragments of two human γ1 heavy chains.Biochem. J. 117: 641–660.
Schanfield, M.S. and Loghem, E. van 1986. Human immunoglobulin allotype. InHandbook of Experimental Immunology, Weir, D.M., ed., 2nd ed., Blackwell Scientific, Oxford, Chap. 94.
Turner, M.W., Martensson, L., Natvig, J.B. and Bennich, H. 1969. Genetic (Gm) antigens associated with subfragments from the Fc fragment of human immunoglobulin G.Nature 221: 1166–1169.
Turner, M.W. 1970. Immunoglobulin allotypes: structure and regulation of their expression. Structural localization of human immunoglobulin allotypes.Biochem. Soc. Trans. 4: 29–33.
Wang, A.C., Shuster, J. and Fudenberg, H.H. 1969. Evolutionary origin of the Gm‘a’ peptide of immunoglobulins.J. Mol. Biol. 41: 83–86.
Wang, A.C., Tung, E. and Fudenberg, H.H. 1980. The Primary structure of a human IgG2 heavy chain: genetic, evolutionary, and functional implications.J. Immunol. 125: 1048–1054.
Westhof, E., Altschuh, D., Moras, D., Bloomer, A.C., Mondragon, A., Klug, A. and Regenmortel, M.H.V. van. 1984. Correlation between segmental mobility and the location of antigenic determinants in proteins.Nature 311: 123–126.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ito, S., Suzuki, K., Miyazaki, T. et al. A key amino acid determining G3m(b) allotypic markers. Jap J Human Genet 36, 179–187 (1991). https://doi.org/10.1007/BF01876582
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1007/BF01876582