Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain.
J Mol Biol
; 292(1): 1-9, 1999 Sep 10.
Article
em En
| MEDLINE
| ID: mdl-10493852
The lymphocyte function-associated antigen (LFA-1) belongs to the family of beta2-integrins and plays an important role in T-cell activation and leukocyte migration to sites of inflammation. We report here that lovastatin, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor intercellular adhesion molecule-1. Using nuclear magnetic resonance spectroscopy and X-ray crystallography we show that the inhibitor binds to a highly conserved domain of the LFA-1 alpha-chain called the I-domain. The first three-dimensional structure of an integrin inhibitor bound to its receptor reveals atomic details for a hitherto unknown mode of LFA-1 inhibition. It also sheds light into possible mechanisms of LFA-1 mediated signalling and will support the design of novel anti-adhesive and immunosuppressive drugs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lovastatina
/
Antígeno-1 Associado à Função Linfocitária
/
Antígenos CD11
Limite:
Humans
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Suíça
País de publicação:
Holanda