Molecular Dynamic Studies of Interferon and Innate Immunity Resistance in MERS CoV Non-Structural Protein 3.
Identifieur interne : 000D60 ( PubMed/Corpus ); précédent : 000D59; suivant : 000D61Molecular Dynamic Studies of Interferon and Innate Immunity Resistance in MERS CoV Non-Structural Protein 3.
Auteurs : Manal Alfuwaires ; Abdallah Altaher ; Mahmoud KandeelSource :
- Biological & pharmaceutical bulletin [ 1347-5215 ] ; 2017.
English descriptors
- KwdEn :
- Catalytic Domain, Coronavirus Infections (immunology), Coronavirus Infections (virology), Cysteine Endopeptidases (metabolism), Humans, Immunity, Innate, Interferons (metabolism), Middle East Respiratory Syndrome Coronavirus (metabolism), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Molecular Dynamics Simulation, Papain, Ubiquitin (metabolism), Ubiquitination, Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , metabolism : Cysteine Endopeptidases, Interferons, Ubiquitin, Viral Nonstructural Proteins.
- immunology : Coronavirus Infections.
- metabolism : Middle East Respiratory Syndrome Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections.
- Catalytic Domain, Humans, Immunity, Innate, Molecular Dynamics Simulation, Papain, Ubiquitination.
Abstract
The new emerging Middle East Respiratory Syndrome Coronavirus (MERS CoV) encodes several resistance proteins against the innate immune response of the host, including interferon (IFN) resistance. Monitoring of the status of such proteins will be important to track viral pathogenicity. In this study, molecular dynamics approaches were used to investigate MERS CoV Non-Structural Protein 3 (NSP3) specific proteins that resist host innate immunity. MERS CoV papain-like protease (Plpro) was more conformationally flexible than Severe Acute Respiratory Syndrome CoV (SARS) CoV Plpro. This flexibility was evident in either the free form or when bound with ubiquitin. There were marked changes in the root-mean-square deviation (RMSD) in the ubiquitin like domain (Ubl) and the fingers subdomain of the catalytic domain of Plpro. An interesting feature is the dynamic change in Ubl, which shows a rigid conformation in the free form of Plpro but is fully flexible upon the binding of ubiquitin. This increased flexibility could be important for the downstream effects of the interaction with other proteins and the inhibition of the innate immunity. Four major residues involved in deubiquitination, L106, P163, R168 and F265, were conserved in all MERS CoVs and differed from other Beta CoVs. These conserved CoV residues were associated with lower deubiquitinating activity and render MERS CoV Plpro with less potent deubiquitinating potential. The number of residues and total interactions with ubiquitin were lower for the MERS CoV Plpro than for the SARS CoV. These factors contribute to the lower deubiquitinating actions of MERS CoV NSP3 and its subsequently lower interaction with the host immune system.
DOI: 10.1248/bpb.b16-00870
PubMed: 28250277
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pubmed:28250277Le document en format XML
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<author><name sortKey="Alfuwaires, Manal" sort="Alfuwaires, Manal" uniqKey="Alfuwaires M" first="Manal" last="Alfuwaires">Manal Alfuwaires</name>
<affiliation><nlm:affiliation>Department of Biology, Faculty of Science, King Faisal University.</nlm:affiliation>
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<author><name sortKey="Altaher, Abdallah" sort="Altaher, Abdallah" uniqKey="Altaher A" first="Abdallah" last="Altaher">Abdallah Altaher</name>
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<author><name sortKey="Kandeel, Mahmoud" sort="Kandeel, Mahmoud" uniqKey="Kandeel M" first="Mahmoud" last="Kandeel">Mahmoud Kandeel</name>
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<author><name sortKey="Altaher, Abdallah" sort="Altaher, Abdallah" uniqKey="Altaher A" first="Abdallah" last="Altaher">Abdallah Altaher</name>
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<term>Humans</term>
<term>Immunity, Innate</term>
<term>Interferons (metabolism)</term>
<term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term>
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<term>Molecular Dynamics Simulation</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term>
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<front><div type="abstract" xml:lang="en">The new emerging Middle East Respiratory Syndrome Coronavirus (MERS CoV) encodes several resistance proteins against the innate immune response of the host, including interferon (IFN) resistance. Monitoring of the status of such proteins will be important to track viral pathogenicity. In this study, molecular dynamics approaches were used to investigate MERS CoV Non-Structural Protein 3 (NSP3) specific proteins that resist host innate immunity. MERS CoV papain-like protease (Plpro) was more conformationally flexible than Severe Acute Respiratory Syndrome CoV (SARS) CoV Plpro. This flexibility was evident in either the free form or when bound with ubiquitin. There were marked changes in the root-mean-square deviation (RMSD) in the ubiquitin like domain (Ubl) and the fingers subdomain of the catalytic domain of Plpro. An interesting feature is the dynamic change in Ubl, which shows a rigid conformation in the free form of Plpro but is fully flexible upon the binding of ubiquitin. This increased flexibility could be important for the downstream effects of the interaction with other proteins and the inhibition of the innate immunity. Four major residues involved in deubiquitination, L106, P163, R168 and F265, were conserved in all MERS CoVs and differed from other Beta CoVs. These conserved CoV residues were associated with lower deubiquitinating activity and render MERS CoV Plpro with less potent deubiquitinating potential. The number of residues and total interactions with ubiquitin were lower for the MERS CoV Plpro than for the SARS CoV. These factors contribute to the lower deubiquitinating actions of MERS CoV NSP3 and its subsequently lower interaction with the host immune system.</div>
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<Abstract><AbstractText>The new emerging Middle East Respiratory Syndrome Coronavirus (MERS CoV) encodes several resistance proteins against the innate immune response of the host, including interferon (IFN) resistance. Monitoring of the status of such proteins will be important to track viral pathogenicity. In this study, molecular dynamics approaches were used to investigate MERS CoV Non-Structural Protein 3 (NSP3) specific proteins that resist host innate immunity. MERS CoV papain-like protease (Plpro) was more conformationally flexible than Severe Acute Respiratory Syndrome CoV (SARS) CoV Plpro. This flexibility was evident in either the free form or when bound with ubiquitin. There were marked changes in the root-mean-square deviation (RMSD) in the ubiquitin like domain (Ubl) and the fingers subdomain of the catalytic domain of Plpro. An interesting feature is the dynamic change in Ubl, which shows a rigid conformation in the free form of Plpro but is fully flexible upon the binding of ubiquitin. This increased flexibility could be important for the downstream effects of the interaction with other proteins and the inhibition of the innate immunity. Four major residues involved in deubiquitination, L106, P163, R168 and F265, were conserved in all MERS CoVs and differed from other Beta CoVs. These conserved CoV residues were associated with lower deubiquitinating activity and render MERS CoV Plpro with less potent deubiquitinating potential. The number of residues and total interactions with ubiquitin were lower for the MERS CoV Plpro than for the SARS CoV. These factors contribute to the lower deubiquitinating actions of MERS CoV NSP3 and its subsequently lower interaction with the host immune system.</AbstractText>
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