Unusual distributions of amino acids in complementarity determining (hypervariable) segments of heavy and light chains of immunoglobulins and their possible roles in specificity of antibody-combining sites

E. A. Kabat, T. T. Wu, H. Bilofsky

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

Using a data bank of sequences of variable regions of immunoglobulin chains to compute incidences of the 20 amino acids at various positions in the complementarity determining segments of light and heavy chains, it was possible to infer that certain amino acids at 13 positions in the light chain and 7 positions in the heavy chain functioned in antibody combining sites as structural elements rather than as contacting or conformationally important residues. These inferences are in good agreement with assignments made by X ray crystallography in almost all instances. The statistical method, however, is independent of X ray crystallography and may permit assigning a role to a position or to a given amino acid at a position in many kinds of antibody combining sites, while an X ray structure provides information only about the antibody being studied. The role of individual amino acids at various positions is greatly affected by insertions or deletions in the complementarity determining segments. The method also permits one to infer that particular amino acids in complementarity determining segments such as histidine and tryptophan are either directly involved in specificity as contacting residues, or exert a conformational influence on such residues. The findings indicate the need for X ray crystallographic studies on immunoglobulins with insertions of different lengths in complementarity determining segments and with sites shown from immunochemical considerations to be grooves or cavities.

Original languageEnglish (US)
Pages (from-to)6609-6616
Number of pages8
JournalJournal of Biological Chemistry
Volume252
Issue number19
StatePublished - 1977

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Unusual distributions of amino acids in complementarity determining (hypervariable) segments of heavy and light chains of immunoglobulins and their possible roles in specificity of antibody-combining sites'. Together they form a unique fingerprint.

Cite this