Structural analysis of affinity maturation: The three-dimensional structures of complexes of an anti-nitrophenol antibody
| Autor: | L. Mario Amzel, Mette Strand, Stacieann C. Yuhasz, Christian S. Parry |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Macromolecular Substances
medicine.drug_class Stereochemistry Molecular Sequence Data Immunology Antibody Affinity Ring (chemistry) Monoclonal antibody Nitrophenols Affinity maturation Mice Antigen medicine Animals Amino Acid Sequence Cloning Molecular Molecular Biology Base Sequence biology Hydrogen bond Chemistry Antibodies Monoclonal Biochemistry biology.protein NIP Immunoglobulin Light Chains Antibody Immunoglobulin Heavy Chains Haptens Hapten |
| Zdroj: | Molecular Immunology. 32:1143-1155 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/0161-5890(95)00063-1 |
| Popis: | Affinity maturation of the immune response to nitrophenol-containing antigens has been extensively investigated. Significant strides made during the past several years with the advent of PCR technology have provided a wealth of biochemical knowledge. Structural investigations of the phenomena have however been limited. We have determined the three-dimensional structure of the Fab fragment of 88C6 12 , an anti-4-hydroxy-3-nitrophenyl acetic acid antibody complexed with the immunizing hapten and with a heteroclitic iodinated hapten. The crystallographic structure of the complexes reveals that the binding is stabilized by a number of hydrogen bonds and extensive van der Waals interactions between the hapten and the antibody. In addition, the Fab binding pocket contains a region of positive electrostatic potential well suited for interaction with the predominant resonance form of the nitrophenyl ring system. The observed heteroclicity towards the iodinated hapten is not a direct result of iodine-protein interactions, but results from the enhanced stability in the iodinated ring of the resonance form that binds the antibody. In addition this investigation provides a rationale for the strong preference for the substitution in the heavy chain from the germline gene encoded Trp 33 to Leu 33 in the mature anti-nitrophenol response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect