Immunoglobulin VH clan and family identity predicts variable domain structure and may influence antigen binding

EMBO J. 1992 Feb;11(2):603-9.

Abstract

Mammalian immunoglobulin VH families can be grouped into three distinct clans based upon sequence conservation in two of the three framework (FR) intervals. Through replacement/silent site substitution analysis, molecular modeling and mathematical evaluation of known immunoglobulin crystal structures, we demonstrate that this conservation reflects preservation of protein sequence and structure. Each clan contains a characteristic FR 1 interval that is solvent-exposed and structurally separated from the antigen binding site. Families within a clan contain their own unique FR 3 interval that is capable of either influencing the conformation of the antigen binding site or interacting directly with antigen. Our results provide a structural context for theories that address differential use of VH families in the immune response.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites, Antibody
  • Fetal Blood / immunology
  • Gene Library
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin Fab Fragments / genetics*
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Heavy Chains / metabolism
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin Variable Region / metabolism
  • Lymphocytes / immunology
  • Mammals
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family*
  • Protein Conformation
  • Sequence Homology, Nucleic Acid

Substances

  • Immunoglobulin Fab Fragments
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region

Associated data

  • GENBANK/D13200
  • GENBANK/D13201
  • GENBANK/D13202
  • GENBANK/D13203
  • GENBANK/L07339
  • GENBANK/M94783
  • GENBANK/M94784
  • GENBANK/M94785
  • GENBANK/X59906
  • GENBANK/X59907
  • GENBANK/X59908
  • GENBANK/X59909
  • GENBANK/X59910
  • GENBANK/X59911
  • GENBANK/X59912
  • GENBANK/X59913
  • GENBANK/X59914
  • GENBANK/X59915
  • GENBANK/X59916
  • GENBANK/X59917
  • GENBANK/X59918
  • GENBANK/X59919
  • GENBANK/X59920
  • GENBANK/X59921
  • GENBANK/X59922
  • GENBANK/X59923
  • GENBANK/X59972
  • GENBANK/X59973
  • GENBANK/X59974
  • GENBANK/X63350