CRYSTAL-STRUCTURE OF THE COMPLEX OF THE VARIABLE DOMAIN OF ANTIBODY D1.3 AND TURKEY EGG-WHITE LYSOZYME - A NOVEL CONFORMATIONAL CHANGE IN ANTIBODY CDR-L3 SELECTS FOR ANTIGEN

The crystal structure of the Fv fragment of the murine monoclonal anti -lysozyme antibody D1.3, complexed with turkey egg-white lysozyme (TEL ), is presented. D1.3 (IgG1, kappa) is a secondary response antibody s pecific for hen egg-white lysozyme (HEL). TEL and HEL are homologous a nd differ in amino acid sequence in the antibody-antigen interface onl y at position 121. The side-chain of HEL residue Gln121 makes a pair o f hydrogen bonds to main-chain atoms of the antibody light chain. In t he D1.3-TEL structure, TEL residue His121 makes only one hydrogen bond with the light chain as a result of 129 degrees and 145 degrees chang e in peptide torsion angles for residues Trp92 and Ser93. Probably as a consequence of this conformational change, the D1.3-TEL association occurs at a much slower rate than the D1.3-HEL association. The D1.S-T EL complex is destabilized with respect to the D1.3-HEL interaction by the loss of two hydrogen bonds, exclusively due to the substitution o f histidine for glutamine. While antibodies of secondary responses are indeed highly specific for antigen, this work demonstrates that by un dergoing subtle conformational change antibodies can still recognize m utated protein antigens, albeit at a cost to affinity. (C) 1996 Academ ic Press Limited