Structural evidence for a constrained conformation of short CDR-L3 in antibodies.
Three Fab structures used as targets in the Antibody Modeling Assessment presented a challenge for modeling CDR-L3 due to deviations from the most typical canonical structure. In all three antibodies CDR-L3 has eight residues, which is one residue shorter than usual, and has a conformation that is rarely observed in crystal structures. We analyzed the sequence and structural determinants of this conformation and found that the "short" CDR-L3 is remarkably rigid and retains the conformation in the interactions with antigens and neighboring CDRs.
Janssen Research & Development, LLC, Spring House, Pennsylvania, 19477.
Alexey
A
Teplyakov
Galina
G
Obmolova
Thomas J
TJ
Malia
Jinquan
J
Luo
Gary L
GL
Gilliland
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D022801:Complementarity Determining Regions / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats
D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007140:Immunoglobulin Fab Fragments
Fab; canonical structure; crystal structure; induced fit; microseed matrix screening