Immunoglobulin V(H) clan and family identity predicts variable domain structure and may influence antigen binding

Academic Article

Abstract

  • Mammalian immunoglobulin V(H) 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 V(H) families in the immune response.
  • Published In

  • EMBO Journal  Journal
  • Author List

  • Kirkham PM; Mortari F; Newton JA; Schroeder HW
  • Start Page

  • 603
  • End Page

  • 609
  • Volume

  • 11
  • Issue

  • 2