The SARS-unique domain (SUD) of SARS-CoV and SARS-CoV-2 interacts with human Paip1 to enhance viral RNA translation.
EMBO J
; 40(11): e102277, 2021 06 01.
Article
em En
| MEDLINE
| ID: mdl-33876849
ABSTRACT
The ongoing outbreak of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) demonstrates the continuous threat of emerging coronaviruses (CoVs) to public health. SARS-CoV-2 and SARS-CoV share an otherwise non-conserved part of non-structural protein 3 (Nsp3), therefore named as "SARS-unique domain" (SUD). We previously found a yeast-2-hybrid screen interaction of the SARS-CoV SUD with human poly(A)-binding protein (PABP)-interacting protein 1 (Paip1), a stimulator of protein translation. Here, we validate SARS-CoV SUDPaip1 interaction by size-exclusion chromatography, split-yellow fluorescent protein, and co-immunoprecipitation assays, and confirm such interaction also between the corresponding domain of SARS-CoV-2 and Paip1. The three-dimensional structure of the N-terminal domain of SARS-CoV SUD ("macrodomain II", Mac2) in complex with the middle domain of Paip1, determined by X-ray crystallography and small-angle X-ray scattering, provides insights into the structural determinants of the complex formation. In cellulo, SUD enhances synthesis of viral but not host proteins via binding to Paip1 in pBAC-SARS-CoV replicon-transfected cells. We propose a possible mechanism for stimulation of viral translation by the SUD of SARS-CoV and SARS-CoV-2.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Polimerase Dependente de RNA
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Regulação Viral da Expressão Gênica
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Fatores de Iniciação de Peptídeos
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Proteínas de Ligação a RNA
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Proteínas não Estruturais Virais
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Coronavírus Relacionado à Síndrome Respiratória Aguda Grave
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Proteases Semelhantes à Papaína de Coronavírus
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SARS-CoV-2
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha