Abstract
Antibody binding site are formed by six hypervariable regions or complementarity determining regions (CDRs). The CDRs, three from the heavy chain and three from the light chain, are known as hypervariable segments and provide a surface, complementary to that of the epitope. In recent work it was found that the amino acids in these positions fulfill different functions: Some play a structural role and others are involved in the specificity-determining function. It is reported here that the frequency of amino acids at hypervariable sites is skewed. By means of an informational algorithm, key physicochemical attributes of the dominant residues were identified for some of those sites. The results for about 1,500 antibodies suggest that approximately 35% of sites involved in the recognition process require only general properties such as composition, volume, and bulk or hydrogen bonding which are satisfied by a small set of amino acids instead of any one particular complementary amino acid.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Chothia C, Lesk AM (1987) Canonical structures for the hypervariable regions of immunoglobulins. J Mol Biol 196:901–918
Go M, Miyazawa S (1980) Relationship between mutability, polarity and exteriority of amino acid residues in protein evolution. Int J Peptide Protein Res 15:211–224
Grantham R (1974) Amino acid difference formula to help explain protein evolution. Science 185:862–864
Kabat EA, Wu TT, Bilofsky H (1977) Unusual distributions of amino acids in complementary determining (hypervariable) segments of heavy and light chains of immunoglobulins and their possible roles in specificity of antibody-combining sites. J Biol Chem 252:6609–6616
Kabat EA, Wu TT, Perry HM, Gottesman KS, Foeller C (1991) Sequences of proteins of immunological interest, 5th ed National Institutes of Health, Bethesda, MD
Lara-Ochoa F, Vargas-Madrazo E, Jiménez-Montaño MA, Almagro JC (1993) BioSystems (in press)
Lim WA, Sauer RT (1989) Alternative packing arrangement in the hydrophobic core of proteins. Nature 339:31–36
Mian IS, Bradwell AR, Olson AJ (1991) Structure, function and properties of antibody binding sites. J Mol Biol 217:133–151
Ohno S, Mori N, Matsunaga T (1985) Antigen-binding specificities of antibodies are primarily determined by seven residues of Vh. Proc Natl Acad Sci USA 82:2945–2949
Padlan EA (1990) On the nature of antibody combining sites: Unusual structural features that may confer on these sites an enhanced capacity for binding ligands. Proteins 7:112–124
Quinlan JR (1983) Learning efficient classification procedures and their application to chess and games. In: Michalski RS, Carbonell JG, Mitchell TM (eds). Machine learning: an artificial intelligence approach, vol I. Morgan Kaufmann, San Mateo, CA, pp 463–482
Shenkin PS, Erman B, Mastrandrea LD (1991) Information-theoretical entropy as a measure of sequence variability. Proteins 9:154–178
Sneath PHA (1966) Relations between structure and biological activity in peptides. J Theor Biol 12:157–195
Spiegel MR (1975) Probability and statistics. McGraw-Hill Book, New York
Tonegawa S (1983) Somatic generation of antibody diversity. Nature 302:575–581
Vargas-Madrazo E, Almagro JC, Lara-Ochoa F, Jiménez-Montaño MA (1992) Proceedings of the seventh Panamerican biochemical congress. Ixtapa, México, September 27–October 2
Wu TT, Kabat EA (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for the antibody complementarity. J Exp Med 132:211–250
Zimmerman JM, Eliezer N, Simha R (1968) The characterization of amino acid sequences in proteins by statistical methods. J Theor Biol 21:170–201
Author information
Authors and Affiliations
Additional information
Correspondence to: E. Vargas-Madrazo
Rights and permissions
About this article
Cite this article
Vargas-Madrazo, E., Lara-Ochoa, F. & Jiménez-Montaño, M. A skewed distribution of amino acids at recognition sites of the hypervariable region of immunoglobulins. J Mol Evol 38, 100–104 (1994). https://doi.org/10.1007/BF00175497
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00175497