Three-Dimensional Structure of Fab R19.9, a Monoclonal Murine Antibody Specific for the p-azobenzenearsonate Group

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989, Vol.86 (2), p.607-611
• Main Authors: M.-B. Lascombe, Alzari, P. M., Boulot, G., Saludjian, P., Tougard, P., Berek, C., Haba, S., Rosen, E. M., Nisonoff, A., Poljak, R. J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; Antibodies, Monoclonal; Antibodies, Monoclonal - analysis; Antibodies, Monoclonal - genetics; Antigens; Azo Compounds; Azo Compounds - immunology; Base Sequence; Biochemistry, Molecular Biology; Bioinformatics; Biological and medical sciences; Biological Physics; Cellular Biology; Chemical Sciences; Computer Science; Cristallography; Crystallization; Crystallography; Electron density; Fundamental and applied biological sciences. Psychology; Immunoglobulin Fab Fragments; Immunoglobulin Fab Fragments - analysis; Immunoglobulin Fab Fragments - genetics; Immunoglobulin Variable Region; Immunoglobulin Variable Region - analysis; Immunoglobulin Variable Region - genetics; Life Sciences; Mice; Molecular biophysics; Molecular Sequence Data; Molecular Structure; Molecules; Monoclonal antibodies; Nucleotides; p-Azobenzenearsonate; p-Azobenzenearsonate - immunology; Physics; Protein Conformation; Solvents; Structural Biology; Structure in molecular biology; Tridimensional structure; X-Ray Diffraction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.2.607

The crystal structure of Fab R19.9, derived from an anti-p-azobenzenearsonate monoclonal antibody, has been determined and refined to 2.8- angstrom resolution by x-ray crystallographic techniques. Monoclonal antibody R19.9 (IgG2bκ ) shares some idiotopes with a major idiotype (CRIA) associated with A/J anti-p-azobenzenearsonate antibodies. The amino acid sequences of the variable (V) parts of the heavy (VH) and light (VL) polypeptide chains of monoclonal antibody R19.9 were determined through nucleotide sequencing of their mRNAs. The VL region is very similar to that of CRIA-positive anti-p-azobenzenearsonate antibodies as is VH, except for its third complementarity-determining region, which is three amino acids longer; it makes a loop, unique to R19.9, that protrudes into the solvent. A large number of tyrosine residues in the complementarity-determining region of VH and VL, with their side chains pointing towards the solvent, may have an important function in antigen binding.