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In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe pneumonia-like symptoms and is still pose a significant threat to global public health. A key component in the virulence of MERS-CoV is the Spike (S) protein, which binds with the host membrane receptor dipeptidyl peptidase 4 (DPP...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515610/ https://www.ncbi.nlm.nih.gov/pubmed/36188214 http://dx.doi.org/10.3389/fmolb.2022.933553 |
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author | Rhoades, Raina Sobitan, Adebiyi Mahase, Vidhyanand Gebremedhin, Brhan Tang, Qiyi Rawat, Danda Cao, Hongbao Teng, Shaolei |
author_facet | Rhoades, Raina Sobitan, Adebiyi Mahase, Vidhyanand Gebremedhin, Brhan Tang, Qiyi Rawat, Danda Cao, Hongbao Teng, Shaolei |
author_sort | Rhoades, Raina |
collection | PubMed |
description | Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe pneumonia-like symptoms and is still pose a significant threat to global public health. A key component in the virulence of MERS-CoV is the Spike (S) protein, which binds with the host membrane receptor dipeptidyl peptidase 4 (DPP4). The goal of the present investigation is to examine the effects of missense mutations in the MERS-CoV S protein on protein stability and binding affinity with DPP4 to provide insight that is useful in developing vaccines to prevent coronavirus infection. We utilized a saturation mutagenesis approach to simulate all possible mutations in the MERS-CoV full-length S, S Receptor Binding Domain (RBD) and DPP4. We found the mutations in MERS-CoV S protein residues, G552, C503, C526, N468, G570, S532, S451, S419, S465, and S435, affect protein stability. We identified key residues, G538, E513, V555, S557, L506, L507, R511, M452, D537, and S454 in the S protein RBD region are important in the binding of MERS-CoV S protein to the DPP4 receptor. We investigated the effects of MERS-CoV S protein viral mutations on protein stability and binding affinity. In addition, we studied all DPP4 mutations and found the functional substitution R336T weakens both DPP4 protein stability and S-DPP4 binding affinity. We compared the S protein structures of MERS-CoV, SARS-CoV, and SARS-CoV-2 viruses and identified the residues like C526, C383, and N468 located in equivalent positions of these viruses have effects on S protein structure. These findings provide further information on how mutations in coronavirus S proteins effect protein function. |
format | Online Article Text |
id | pubmed-9515610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95156102022-09-29 In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein Rhoades, Raina Sobitan, Adebiyi Mahase, Vidhyanand Gebremedhin, Brhan Tang, Qiyi Rawat, Danda Cao, Hongbao Teng, Shaolei Front Mol Biosci Molecular Biosciences Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe pneumonia-like symptoms and is still pose a significant threat to global public health. A key component in the virulence of MERS-CoV is the Spike (S) protein, which binds with the host membrane receptor dipeptidyl peptidase 4 (DPP4). The goal of the present investigation is to examine the effects of missense mutations in the MERS-CoV S protein on protein stability and binding affinity with DPP4 to provide insight that is useful in developing vaccines to prevent coronavirus infection. We utilized a saturation mutagenesis approach to simulate all possible mutations in the MERS-CoV full-length S, S Receptor Binding Domain (RBD) and DPP4. We found the mutations in MERS-CoV S protein residues, G552, C503, C526, N468, G570, S532, S451, S419, S465, and S435, affect protein stability. We identified key residues, G538, E513, V555, S557, L506, L507, R511, M452, D537, and S454 in the S protein RBD region are important in the binding of MERS-CoV S protein to the DPP4 receptor. We investigated the effects of MERS-CoV S protein viral mutations on protein stability and binding affinity. In addition, we studied all DPP4 mutations and found the functional substitution R336T weakens both DPP4 protein stability and S-DPP4 binding affinity. We compared the S protein structures of MERS-CoV, SARS-CoV, and SARS-CoV-2 viruses and identified the residues like C526, C383, and N468 located in equivalent positions of these viruses have effects on S protein structure. These findings provide further information on how mutations in coronavirus S proteins effect protein function. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9515610/ /pubmed/36188214 http://dx.doi.org/10.3389/fmolb.2022.933553 Text en Copyright © 2022 Rhoades, Sobitan, Mahase, Gebremedhin, Tang, Rawat, Cao and Teng. 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 | Molecular Biosciences Rhoades, Raina Sobitan, Adebiyi Mahase, Vidhyanand Gebremedhin, Brhan Tang, Qiyi Rawat, Danda Cao, Hongbao Teng, Shaolei In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein |
title | In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein |
title_full | In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein |
title_fullStr | In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein |
title_full_unstemmed | In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein |
title_short | In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein |
title_sort | in-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515610/ https://www.ncbi.nlm.nih.gov/pubmed/36188214 http://dx.doi.org/10.3389/fmolb.2022.933553 |
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