Structural insights into the evolution of an antibody combining site.
Science
; 276(5319): 1665-9, 1997 Jun 13.
Article
em En
| MEDLINE
| ID: mdl-9180069
ABSTRACT
The crystal structures of a germline antibody Fab fragment and its complex with hapten have been solved at 2.1 A resolution. These structures are compared with the corresponding crystal structures of the affinity-matured antibody, 48G7, which has a 30,000 times higher affinity for hapten as a result of nine replacement somatic mutations. Significant changes in the configuration of the combining site occur upon binding of hapten to the germline antibody, whereas hapten binds to the mature antibody by a lock-and-key fit mechanism. The reorganization of the combining site that was nucleated by hapten binding is further optimized by somatic mutations that occur up to 15 from bound hapten. These results suggest that the binding potential of the primary antibody repertoire may be significantly expanded by the ability of germline antibodies to adopt more than one combining-site configuration, with both antigen binding and somatic mutation stabilizing the configuration with optimal hapten complementarity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sítios de Ligação de Anticorpos
/
Fragmentos Fab das Imunoglobulinas
/
Anticorpos Catalíticos
/
Evolução Molecular
Idioma:
En
Revista:
Science
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos