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

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 structure...

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Bibliographic Details
Published in:The EMBO journal 1992-02, Vol.11 (2), p.603-609
Main Authors: Kirkham, P.M., Mortari, F., Newton, J.A., Schroeder, H.W.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Binding Sites, Antibody
Biological and medical sciences
Fetal Blood - immunology
Fundamental and applied biological sciences. Psychology
Gene Library
Genes, Immunoglobulin
Genes. Genome
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 and cellular biology
Molecular genetics
Molecular Sequence Data
Multigene Family
Protein Conformation
Sequence Homology, Nucleic Acid
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1002/j.1460-2075.1992.tb05092.x