Structural patterns at residue positions 9, 18, 67 and 82 in the VH framework regions of human and murine immunoglobulins

Abstract

VH framework regions of human and mouse immunoglobulins display three characteristic patterns in the conformation of the main polypeptide chain and side-chains at residue positions 9, 18, 67 and 82. These structural patterns are associated with the amino acid sequence at positions 9 and 67. Human and murine VH sequences show a strong correlation between the occurrence of Gly at position 9 and Phe at position 67 in VH subgroup III, and the frequent occurrence of Pro, Ala or Ser at position 9 and a non-aromatic residue at position 67 in other VH subgroups. Variations in VH framework segments have been shown to be of importance in procedures to humanize monoclonal murine antibodies and may be involved in the conformation of epitopes recognized by anti-VH antibodies. The structural patterns described here can be expected to influence the results of rotation and translation search functions in the crystallographic structure determination of Fab and Fv fragments by the molecular replacement method.