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Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G...

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Autores principales: Hamza, Abu, Samad, Abdus, Parray, Zahoor Ahmad, Ara, Sajda, Ahmed, Anwar, Almajhdi, Fahad N., Hussain, Tajamul, Islam, Asimul, Parveen, Shama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880246/
https://www.ncbi.nlm.nih.gov/pubmed/35216066
http://dx.doi.org/10.3390/ijms23041950
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author Hamza, Abu
Samad, Abdus
Parray, Zahoor Ahmad
Ara, Sajda
Ahmed, Anwar
Almajhdi, Fahad N.
Hussain, Tajamul
Islam, Asimul
Parveen, Shama
author_facet Hamza, Abu
Samad, Abdus
Parray, Zahoor Ahmad
Ara, Sajda
Ahmed, Anwar
Almajhdi, Fahad N.
Hussain, Tajamul
Islam, Asimul
Parveen, Shama
author_sort Hamza, Abu
collection PubMed
description Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G protein. In the present study, the effect of amino acid substitution on the structure and stability of the ectodomain G protein was studied. Further, it was investigated whether mutation (K117A) in the CX3C motif of G protein alters the binding with heparan sulfate. The point mutation significantly affects the conformational stability of the G protein. The mutant protein showed a low binding affinity with heparan sulfate as compared to the wild-type G protein, as determined by fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking studies. The low binding affinity and decreased stability suggested that this mutation may play an important role in prevention of attachment of virion to the host cell receptors. Collectively, this investigation suggests that mutation in the CX3C motif of G protein may likely improve the efficacy and safety of the RSV vaccine.
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spelling pubmed-88802462022-02-26 Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study Hamza, Abu Samad, Abdus Parray, Zahoor Ahmad Ara, Sajda Ahmed, Anwar Almajhdi, Fahad N. Hussain, Tajamul Islam, Asimul Parveen, Shama Int J Mol Sci Article Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G protein. In the present study, the effect of amino acid substitution on the structure and stability of the ectodomain G protein was studied. Further, it was investigated whether mutation (K117A) in the CX3C motif of G protein alters the binding with heparan sulfate. The point mutation significantly affects the conformational stability of the G protein. The mutant protein showed a low binding affinity with heparan sulfate as compared to the wild-type G protein, as determined by fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking studies. The low binding affinity and decreased stability suggested that this mutation may play an important role in prevention of attachment of virion to the host cell receptors. Collectively, this investigation suggests that mutation in the CX3C motif of G protein may likely improve the efficacy and safety of the RSV vaccine. MDPI 2022-02-09 /pmc/articles/PMC8880246/ /pubmed/35216066 http://dx.doi.org/10.3390/ijms23041950 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hamza, Abu
Samad, Abdus
Parray, Zahoor Ahmad
Ara, Sajda
Ahmed, Anwar
Almajhdi, Fahad N.
Hussain, Tajamul
Islam, Asimul
Parveen, Shama
Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study
title Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study
title_full Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study
title_fullStr Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study
title_full_unstemmed Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study
title_short Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study
title_sort mutation in the cx3c motif of g protein disrupts its interaction with heparan sulfate: a calorimetric, spectroscopic, and molecular docking study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880246/
https://www.ncbi.nlm.nih.gov/pubmed/35216066
http://dx.doi.org/10.3390/ijms23041950
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