Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Exp Med ; 213(13): 2885-2896, 2016 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-27821549

RESUMO

Mycolactone, an immunosuppressive macrolide released by the human pathogen Mycobacterium ulcerans, was previously shown to impair Sec61-dependent protein translocation, but the underlying molecular mechanism was not identified. In this study, we show that mycolactone directly targets the α subunit of the Sec61 translocon to block the production of secreted and integral membrane proteins with high potency. We identify a single-amino acid mutation conferring resistance to mycolactone, which localizes its interaction site near the lumenal plug of Sec61α. Quantitative proteomics reveals that during T cell activation, mycolactone-mediated Sec61 blockade affects a selective subset of secretory proteins including key signal-transmitting receptors and adhesion molecules. Expression of mutant Sec61α in mycolactone-treated T cells rescued their homing potential and effector functions. Furthermore, when expressed in macrophages, the mycolactone-resistant mutant restored IFN-γ receptor-mediated antimicrobial responses. Thus, our data provide definitive genetic evidence that Sec61 is the host receptor mediating the diverse immunomodulatory effects of mycolactone and identify Sec61 as a novel regulator of immune cell functions.


Assuntos
Macrolídeos/farmacologia , Receptores de Interferon/imunologia , Canais de Translocação SEC/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/imunologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Adesão Celular/imunologia , Humanos , Células Jurkat , Receptores de Interferon/genética , Canais de Translocação SEC/genética , Canais de Translocação SEC/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Receptor de Interferon gama
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...