Conformational similarity and systematic displacement of complementarity determining region loops in high resolution antibody x-ray structures.
Comparison of seven high resolution x-ray structures shows that the conformations of canonical complementarity determining region (CDR) loops, which are shared by these antibodies, are very similar. However, large spatial displacements (up to 2.7 A) of the essentially identical CDR loops become evident when the antibody beta-sheet frameworks, to which the loops are attached, are least-squares superposed. The loop displacements follow, and amplify, small positional differences in framework/loop splice points. Intradomain structural variability and, to a lesser extent, domain-domain orientation appear to cause the observed loop divergences. The results suggest that the selection of framework regions for loop grafting procedures is more critical than previously thought.
Bajorath
J
J
Bristol-Myers Squibb Research Institute, Seattle, Washington 98121, USA.
Harris
L
L
Novotny
J
J
D000595:Amino Acid Sequence; D001666:Binding Sites, Antibody; D018360:Crystallography, X-Ray; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000648:ultrastructure; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000648:ultrastructure; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000648:ultrastructure; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains