Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein
| Autor: | Genera, Mariano, Quioc-Salomon, Barbara, Nourisson, Antonin, Colcombet-Cazenave, Baptiste, Haouz, Ahmed, Mechaly, Ariel, Matondo, Mariette, Duchateau, Magalie, König, Alexander, Windisch, Marc, Neuveut, Christine, Wolff, Nicolas, Caillet-Saguy, Célia |
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| Přispěvatelé: | ED 515 - Complexité du vivant, Sorbonne Université (SU), Récepteurs Canaux - Channel Receptors, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hépacivirus et Immunité innée, Université Paris Diderot - Paris 7 (UPD7), Cristallographie (Plateforme) - Crystallography (Platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Plateforme de Protéomique / Proteomics platform, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP), MG is part of the Pasteur-Paris University (PPU) International PhD Program. BQS was supported by ANRS. BCC was supported by the Ministère de l'Enseignement Supérieur et de la Recherche., We thank the staff of the crystallography platform at Institut Pasteur for carrying out robot-driven crystallization screening. We thank Sébastien Brûlé and Bertrand Raynal from the Institut Pasteur molecular biophysics platform for the design and analysis of the AUC experiment. We thank Bruno Vitorge from the Institut Pasteur biological NMR technological platform for help with NMR experiments. We acknowledge synchrotron SOLEIL (Saint-Aubin, France) for granting access to their facility and the staff of Proxima1 for helpful assistance during the data collection. We thank Lauriane Lecoq and Anja Böckmann for the pRSF-T7-HBc183opt plasmid and the advices to produce HBc., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Hepatitis B virus
Molecular biology Science viruses PDZ Domains Biochemistry Article Capsid [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Structure determination Biophysical methods Viral Core Proteins Biological techniques Protein Tyrosine Phosphatase Non-Receptor Type 3 High-throughput screening virus diseases Proteins Hepatitis B Hepatitis B Core Antigens digestive system diseases [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Medicine Tyrosine Protein Tyrosine Phosphatases |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2021, 11, pp.944. ⟨10.1038/s41598-020-79580-9⟩ Scientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) Scientific Reports, 2021, 11, pp.944. ⟨10.1038/s41598-020-79580-9⟩ |
| ISSN: | 2045-2322 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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