Tsg101 chaperone function revealed by HIV-1 assembly inhibitors.
Nat Commun
; 8(1): 1391, 2017 11 09.
Article
em En
| MEDLINE
| ID: mdl-29123089
ABSTRACT
HIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structural precursor polyprotein, Gag, allows the recruitment of Tsg101 and other ESCRTs to virus assembly sites where they mediate budding. It is not known how or even whether the UEV Ub binding function contributes to virus production. Here, we report that disruption of UEV Ub binding by commonly used drugs arrests assembly at an early step distinct from the late stage involving PTAP binding disruption. NMR reveals that the drugs form a covalent adduct near the Ub-binding pocket leading to the disruption of Ub, but not PTAP binding. We conclude that the Ub-binding pocket has a chaperone function involved in bud initiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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HIV-1
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Montagem de Vírus
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Proteínas de Ligação a DNA
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Produtos do Gene gag do Vírus da Imunodeficiência Humana
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Complexos Endossomais de Distribuição Requeridos para Transporte
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Liberação de Vírus
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article