A short sequence in the tail of SARS-CoV-2 envelope protein controls accessibility of its PDZ Binding Motif to the cytoplasm

Benoit Neitthoffer (1) , Flavio Alvarez (2) , Florence Larrous (3) , Célia Caillet-Saguy (2) , Sandrine Etienne-Manneville (1) , Batiste Boëda (1)

1 Polarité cellulaire, Migration et Cancer - Cell Polarity, Migration and Cancer
2 Récepteurs Canaux - Channel Receptors
3 Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology

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 neither by 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.

Domaines: Sciences du Vivant [q-bio]

Benoit Neitthoffer, Flavio Alvarez, Florence Larrous, Célia Caillet-Saguy, Sandrine Etienne-Manneville, et al.. A short sequence in the tail of SARS-CoV-2 envelope protein controls accessibility of its PDZ Binding Motif to the cytoplasm. 2023. ⟨pasteur-04257862⟩