Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein

Abstract Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for intera...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mariano Genera, Barbara Quioc-Salomon, Antonin Nourisson, Baptiste Colcombet-Cazenave, Ahmed Haouz, Ariel Mechaly, Mariette Matondo, Magalie Duchateau, Alexander König, Marc P. Windisch, Christine Neuveut, Nicolas Wolff, Célia Caillet-Saguy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1aa13d44608f4a1a8117b0820723178a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1aa13d44608f4a1a8117b0820723178a
record_format	dspace
spelling	oai:doaj.org-article:1aa13d44608f4a1a8117b0820723178a2021-12-02T14:01:35ZMolecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein10.1038/s41598-020-79580-92045-2322https://doaj.org/article/1aa13d44608f4a1a8117b0820723178a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79580-9https://doaj.org/toc/2045-2322Abstract Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for interactions with host PDZ domain-containing proteins. In this work, we focused on the human protein tyrosine phosphatase non-receptor type 3 (PTPN3) and its interaction with HBc. We solved the crystal structure of the PDZ domain of PTPN3 in complex with the PBM of HBc, revealing a network of interactions specific to class I PDZ domains despite the presence of a C-terminal cysteine in this atypical PBM. We further showed that PTPN3 binds the HBc protein within capsids or as a homodimer. We demonstrate that overexpression of PTPN3 significantly affects HBV infection in HepG2 NTCP cells. Finally, we performed proteomics studies on both sides by pull-down assays and screening of a human PDZ domain library. We identified a pool of human PBM-containing proteins that might interact with PTPN3 in cells and that could be in competition with the HBc PBM during infection, and we also identified potential cellular partners of HBc through PDZ-PBM interactions. This study opens up many avenues of future investigations into the pathophysiology of HBV.Mariano GeneraBarbara Quioc-SalomonAntonin NourissonBaptiste Colcombet-CazenaveAhmed HaouzAriel MechalyMariette MatondoMagalie DuchateauAlexander KönigMarc P. WindischChristine NeuveutNicolas WolffCélia Caillet-SaguyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mariano Genera Barbara Quioc-Salomon Antonin Nourisson Baptiste Colcombet-Cazenave Ahmed Haouz Ariel Mechaly Mariette Matondo Magalie Duchateau Alexander König Marc P. Windisch Christine Neuveut Nicolas Wolff Célia Caillet-Saguy Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein
description	Abstract Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for interactions with host PDZ domain-containing proteins. In this work, we focused on the human protein tyrosine phosphatase non-receptor type 3 (PTPN3) and its interaction with HBc. We solved the crystal structure of the PDZ domain of PTPN3 in complex with the PBM of HBc, revealing a network of interactions specific to class I PDZ domains despite the presence of a C-terminal cysteine in this atypical PBM. We further showed that PTPN3 binds the HBc protein within capsids or as a homodimer. We demonstrate that overexpression of PTPN3 significantly affects HBV infection in HepG2 NTCP cells. Finally, we performed proteomics studies on both sides by pull-down assays and screening of a human PDZ domain library. We identified a pool of human PBM-containing proteins that might interact with PTPN3 in cells and that could be in competition with the HBc PBM during infection, and we also identified potential cellular partners of HBc through PDZ-PBM interactions. This study opens up many avenues of future investigations into the pathophysiology of HBV.
format	article
author	Mariano Genera Barbara Quioc-Salomon Antonin Nourisson Baptiste Colcombet-Cazenave Ahmed Haouz Ariel Mechaly Mariette Matondo Magalie Duchateau Alexander König Marc P. Windisch Christine Neuveut Nicolas Wolff Célia Caillet-Saguy
author_facet	Mariano Genera Barbara Quioc-Salomon Antonin Nourisson Baptiste Colcombet-Cazenave Ahmed Haouz Ariel Mechaly Mariette Matondo Magalie Duchateau Alexander König Marc P. Windisch Christine Neuveut Nicolas Wolff Célia Caillet-Saguy
author_sort	Mariano Genera
title	Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein
title_short	Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein
title_full	Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein
title_fullStr	Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein
title_full_unstemmed	Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein
title_sort	molecular basis of the interaction of the human tyrosine phosphatase ptpn3 with the hepatitis b virus core protein
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1aa13d44608f4a1a8117b0820723178a
work_keys_str_mv	AT marianogenera molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT barbaraquiocsalomon molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT antoninnourisson molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT baptistecolcombetcazenave molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT ahmedhaouz molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT arielmechaly molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT mariettematondo molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT magalieduchateau molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT alexanderkonig molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT marcpwindisch molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT christineneuveut molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT nicolaswolff molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein AT celiacailletsaguy molecularbasisoftheinteractionofthehumantyrosinephosphataseptpn3withthehepatitisbviruscoreprotein
_version_	1718392124761702400

Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein

Ejemplares similares