Anatomy of an antibody molecule: structure, kinetics, thermodynamics and mutational studies of the antilysozyme antibody D1.3.

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TitleAnatomy of an antibody molecule: structure, kinetics, thermodynamics and mutational studies of the antilysozyme antibody D1.3.
Publication TypeJournal Article
Year of Publication1998
AuthorsBraden, BC, Goldman, ER, Mariuzza, RA, Poljak, RJ
JournalImmunol Rev
Volume163
Pagination45-57
Date Published1998 Jun
ISSN0105-2896
KeywordsAlanine, Animals, Antibodies, Crystallography, X-Ray, Humans, Immunoglobulin Fragments, Immunoglobulin Variable Region, Kinetics, Muramidase, Mutagenesis, Site-Directed, Protein Conformation, Thermodynamics
Abstract

Using site-directed mutagenesis, x-ray crystallography, microcalorimetric, equilibrium sedimentation and surface plasmon resonance detection techniques, we have examined the structure of an antibody-antigen complex and the structural and thermodynamic consequences of removing specific hydrogen bonds and van der Waals interactions in the antibody-antigen interface. These observations show that the complex is considerably tolerant, both structurally and thermodynamically, to the truncation of antibody and antigen side chains that form contacts. Alterations in interface solvent structure for two of the mutant complexes appear to compensate for the unfavorable enthalpy changes when antibody-antigen interactions are removed. These changes in solvent structure, along with the increased mobility of side chains near the mutation site, probably contribute to the observed entropy compensation. In concert, data from structural studies, reaction rates, calorimetric measurements and site directed mutations are beginning to detail the nature of antibody-protein antigen interactions.

Alternate JournalImmunol. Rev.
PubMed ID9700501
Grant ListGM5280 / GM / NIGMS NIH HHS / United States