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Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins

The C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein E contains a PBM (PDZ-binding motif) targeting PDZ (PSD-95/Dlg/ZO-1) domains, which is identical to the PBM of SARS-CoV. The latter is involved in the pathogenicity of the virus. Recently, we identified 10 hum...

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Autores principales: Zhu, Yanlei, Alvarez, Flavio, Wolff, Nicolas, Mechaly, Ariel, Brûlé, Sébastien, Neitthoffer, Benoit, Etienne-Manneville, Sandrine, Haouz, Ahmed, Boëda, Batiste, Caillet-Saguy, Célia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909127/
https://www.ncbi.nlm.nih.gov/pubmed/35283834
http://dx.doi.org/10.3389/fmicb.2022.829094
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author Zhu, Yanlei
Alvarez, Flavio
Wolff, Nicolas
Mechaly, Ariel
Brûlé, Sébastien
Neitthoffer, Benoit
Etienne-Manneville, Sandrine
Haouz, Ahmed
Boëda, Batiste
Caillet-Saguy, Célia
author_facet Zhu, Yanlei
Alvarez, Flavio
Wolff, Nicolas
Mechaly, Ariel
Brûlé, Sébastien
Neitthoffer, Benoit
Etienne-Manneville, Sandrine
Haouz, Ahmed
Boëda, Batiste
Caillet-Saguy, Célia
author_sort Zhu, Yanlei
collection PubMed
description The C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein E contains a PBM (PDZ-binding motif) targeting PDZ (PSD-95/Dlg/ZO-1) domains, which is identical to the PBM of SARS-CoV. The latter is involved in the pathogenicity of the virus. Recently, we identified 10 human PDZ-containing proteins showing significant interactions with SARS-CoV-2 protein E PBM. We selected several of them involved in cellular junctions and cell polarity (TJP1, PARD3, MLLT4, and LNX2) and MPP5/PALS1 previously shown to interact with SARS-CoV E PBM. Targeting cellular junctions and polarity components is a common strategy by viruses to hijack cell machinery to their advantage. In this study, we showed that these host PDZ domains TJP1, PARD3, MLLT4, LNX2, and MPP5/PALS1 interact in a PBM-dependent manner in vitro and colocalize with the full-length E protein in cellulo, sequestrating the PDZ domains to the Golgi compartment. We solved three crystal structures of complexes between human LNX2, MLLT4, and MPP5 PDZs and SARS-CoV-2 E PBM highlighting its binding preferences for several cellular targets. Finally, we showed different affinities for the PDZ domains with the original SARS-CoV-2 C-terminal sequence containing the PBM and the one of the beta variant that contains a mutation close to the PBM. The acquired mutations in the E protein localized near the PBM might have important effects both on the structure and the ion-channel activity of the E protein and on the host machinery targeted by the variants during the infection.
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spelling pubmed-89091272022-03-11 Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins Zhu, Yanlei Alvarez, Flavio Wolff, Nicolas Mechaly, Ariel Brûlé, Sébastien Neitthoffer, Benoit Etienne-Manneville, Sandrine Haouz, Ahmed Boëda, Batiste Caillet-Saguy, Célia Front Microbiol Microbiology The C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein E contains a PBM (PDZ-binding motif) targeting PDZ (PSD-95/Dlg/ZO-1) domains, which is identical to the PBM of SARS-CoV. The latter is involved in the pathogenicity of the virus. Recently, we identified 10 human PDZ-containing proteins showing significant interactions with SARS-CoV-2 protein E PBM. We selected several of them involved in cellular junctions and cell polarity (TJP1, PARD3, MLLT4, and LNX2) and MPP5/PALS1 previously shown to interact with SARS-CoV E PBM. Targeting cellular junctions and polarity components is a common strategy by viruses to hijack cell machinery to their advantage. In this study, we showed that these host PDZ domains TJP1, PARD3, MLLT4, LNX2, and MPP5/PALS1 interact in a PBM-dependent manner in vitro and colocalize with the full-length E protein in cellulo, sequestrating the PDZ domains to the Golgi compartment. We solved three crystal structures of complexes between human LNX2, MLLT4, and MPP5 PDZs and SARS-CoV-2 E PBM highlighting its binding preferences for several cellular targets. Finally, we showed different affinities for the PDZ domains with the original SARS-CoV-2 C-terminal sequence containing the PBM and the one of the beta variant that contains a mutation close to the PBM. The acquired mutations in the E protein localized near the PBM might have important effects both on the structure and the ion-channel activity of the E protein and on the host machinery targeted by the variants during the infection. Frontiers Media S.A. 2022-02-23 /pmc/articles/PMC8909127/ /pubmed/35283834 http://dx.doi.org/10.3389/fmicb.2022.829094 Text en Copyright © 2022 Zhu, Alvarez, Wolff, Mechaly, Brûlé, Neitthoffer, Etienne-Manneville, Haouz, Boëda and Caillet-Saguy. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhu, Yanlei
Alvarez, Flavio
Wolff, Nicolas
Mechaly, Ariel
Brûlé, Sébastien
Neitthoffer, Benoit
Etienne-Manneville, Sandrine
Haouz, Ahmed
Boëda, Batiste
Caillet-Saguy, Célia
Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins
title Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins
title_full Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins
title_fullStr Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins
title_full_unstemmed Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins
title_short Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins
title_sort interactions of severe acute respiratory syndrome coronavirus 2 protein e with cell junctions and polarity psd-95/dlg/zo-1-containing proteins
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909127/
https://www.ncbi.nlm.nih.gov/pubmed/35283834
http://dx.doi.org/10.3389/fmicb.2022.829094
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