title: 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.
abstract: 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 specific for hen egg-white lysozyme (HEL). TEL and HEL are homologous and differ in amino acid sequence in the antibody-antigen interface only at position 121. The side-chain of HEL residue Gln121 makes a pair of hydrogen bonds to main-chain atoms of the antibody light chain. In the D1.3-TEL structure, TEL residue His121 makes only one hydrogen bond with the light chain as a result of 129 degree and 145 degree change 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 D1.3-TEL complex is destabilized with respect to the D1.3-HEL interaction by the loss of two hydrogen bonds, exclusively due to the substitution of histidine for glutamine. While antibodies of secondary responses are indeed highly specific for antigen, this work demonstrates that by undergoing subtle conformational change antibodies can still recognize mutated protein antigens, albeit at a cost to affinity.
authors.affiliation: Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville MD 20850, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Braden
authors.forename: B A
authors.initials: BA
authors.lastname: Fields
authors.forename: X
authors.initials: X
authors.lastname: Ysern
authors.forename: F A
authors.initials: FA
authors.lastname: Goldbaum
authors.forename: W
authors.initials: W
authors.lastname: Dall'Acqua
authors.forename: F P
authors.initials: FP
authors.lastname: Schwarz
authors.forename: R J
authors.initials: RJ
authors.lastname: Poljak
authors.forename: R A
authors.initials: RA
authors.lastname: Mariuzza
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D001666:Binding Sites, Antibody; D002645:Chickens; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D005973:Glutamine / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D007128:Immunoglobulin Fragments / Q000737:chemistry* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics; D014422:Turkeys
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; C055966:immunoglobulin Fv; D005973:Glutamine; D006639:Histidine; D009113:Muramidase