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. 1992 Feb;11(2):603–609. doi: 10.1002/j.1460-2075.1992.tb05092.x

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

P M Kirkham 1, F Mortari 1, J A Newton 1, H W Schroeder Jr 1
PMCID: PMC556492  PMID: 1537339

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.

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Selected References

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