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ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis.
J Virol
September 2024
Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, Florida, USA.
Interferon (IFN)-stimulated gene 15 (ISG15), a ubiquitin-like protein, is covalently conjugated to host immune proteins such as MDA5 and IRF3 in a process called ISGylation, thereby promoting type I IFN induction to limit the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, whether SARS-CoV-2 proteins can be directly targeted for ISGylation remains elusive. In this study, we identified the nucleocapsid (N) protein of SARS-CoV-2 as a major substrate of ISGylation catalyzed by the host E3 ligase HERC5; however, N ISGylation is readily removed through deISGylation by the papain-like protease (PLpro) activity of NSP3.
View Article and Find Full Text PDFISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis.
bioRxiv
May 2024
Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL 34987, USA.
Interferon (IFN)-stimulated gene 15 (ISG15), a ubiquitin-like protein, is covalently conjugated to host (immune) proteins such as MDA5 and IRF3 in a process called ISGylation, thereby limiting the replication of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, whether SARS-CoV-2 proteins can be directly targeted for ISGylation remains elusive. In this study, we identified the nucleocapsid (N) protein of SARS-CoV-2 as a major substrate of ISGylation catalyzed by the host E3 ligase HERC5; however, N ISGylation is readily removed through de-ISGylation by the papain-like protease (PLpro) activity of NSP3.
View Article and Find Full Text PDFInterpol review of fire investigation 2016-2019.
Forensic Sci Int Synerg
March 2020
École des Sciences Criminelles, Université de Lausanne, Batochime, 1015, Lausanne-Dorigny, Switzerland.
This review paper covers the forensic-relevant literature in fire analysis and investigation sciences from 2016 to 2019 as a part of the 19th Interpol International Forensic Science Managers Symposium. The review papers are also available at the Interpol website at: https://www.interpol.
View Article and Find Full Text PDFMesencephalic astrocyte-derived neurotrophic factor is an ER-resident chaperone that protects against reductive stress in the heart.
J Biol Chem
May 2020
San Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, California, USA
We have previously demonstrated that ischemia/reperfusion (I/R) impairs endoplasmic reticulum (ER)-based protein folding in the heart and thereby activates an unfolded protein response sensor and effector, activated transcription factor 6α (ATF6). ATF6 then induces mesencephalic astrocyte-derived neurotrophic factor (MANF), an ER-resident protein with no known structural homologs and unclear ER function. To determine MANF's function in the heart , here we developed a cardiomyocyte-specific MANF-knockdown mouse model.
View Article and Find Full Text PDFAs part of the G-protein coupled receptor (GPCR) family, metabotropic glutamate (mGlu) receptors play an important role as drug targets of cognitive diseases. Selective allosteric modulators of mGlu subtype 5 (mGlu) have the potential to alleviate symptoms of numerous central nervous system disorders such as schizophrenia in a more targeted fashion. Multiple mGlu positive allosteric modulators (PAMs), such as 1-(3-fluorophenyl)--((3-fluorophenyl)-methylideneamino)-methanimine (DFB), 3-cyano--(1,3-diphenyl-1-pyrazol-5-yl)-benzamide (CDPPB), and 4-nitro--(1,3-diphenyl-1-pyrazol-5-yl)-benzamide (VU-29), exert their actions by binding to a defined allosteric site on mGlu located in the seven-transmembrane domain (7TM) and shared by mGlu negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)-pyridine (MPEP).
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