Your browser doesn't support javascript.
loading
A short sequence in the tail of SARS-CoV-2 envelope protein controls accessibility of its PDZ-binding motif to the cytoplasm.
Neitthoffer, Benoit; Alvarez, Flavio; Larrous, Florence; Caillet-Saguy, Célia; Etienne-Manneville, Sandrine; Boëda, Batiste.
Afiliação
  • Neitthoffer B; Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Université Paris Cité, Equipe Labellisée Ligue Contre le Cancer, Paris, France.
  • Alvarez F; Laboratory Channel Receptors, UMR CNRS 3571, Institut Pasteur, Université Paris Cité, Paris, France.
  • Larrous F; Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Université Paris Cité, Paris, France.
  • Caillet-Saguy C; Laboratory Channel Receptors, UMR CNRS 3571, Institut Pasteur, Université Paris Cité, Paris, France.
  • Etienne-Manneville S; Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Université Paris Cité, Equipe Labellisée Ligue Contre le Cancer, Paris, France.
  • Boëda B; Cell Polarity, Migration and Cancer Unit, Institut Pasteur, UMR3691 CNRS, Université Paris Cité, Equipe Labellisée Ligue Contre le Cancer, Paris, France. Electronic address: boeda@pasteur.fr.
J Biol Chem ; 300(1): 105575, 2024 Jan.
Article em En | MEDLINE | ID: mdl-38110034
ABSTRACT
The carboxy-terminal tail of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope protein (E) contains a PDZ-binding motif (PBM) which is crucial for coronavirus pathogenicity. During SARS-CoV-2 infection, the viral E protein is expressed within the Golgi apparatus membrane of host cells with its PBM facing the cytoplasm. In this work, we study the molecular mechanisms controlling the presentation of the PBM to host PDZ (PSD-95/Dlg/ZO-1) domain-containing proteins. We show that at the level of the Golgi apparatus, the PDZ-binding motif of the E protein is not detected by E C-terminal specific antibodies nor by the PDZ domain-containing protein-binding partner. Four alanine substitutions upstream of the PBM in the central region of the E protein tail is sufficient to generate immunodetection by anti-E antibodies and trigger robust recruitment of the PDZ domain-containing protein into the Golgi organelle. Overall, this work suggests that the presentation of the PBM to the cytoplasm is under conformational regulation mediated by the central region of the E protein tail and that PBM presentation probably does not occur at the surface of Golgi cisternae but likely at post-Golgi stages of the viral cycle.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citoplasma / Proteínas do Envelope de Coronavírus / SARS-CoV-2 Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citoplasma / Proteínas do Envelope de Coronavírus / SARS-CoV-2 Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França