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Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions

The global burden of disease caused by a respiratory syncytial virus (RSV) is becoming more widely recognized in young children and adults. Heparan sulfate helps in attaching the virion through G protein with the host cell membrane. In this study, we examined the structural changes of ectodomain G p...

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Autores principales: Hamza, Abu, Samad, Abdus, Imam, Md. Ali, Faizan, Md. Imam, Ahmed, Anwar, Almajhdi, Fahad N., Hussain, Tajamul, Islam, Asimul, Parveen, Shama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658883/
https://www.ncbi.nlm.nih.gov/pubmed/34885979
http://dx.doi.org/10.3390/molecules26237398
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author Hamza, Abu
Samad, Abdus
Imam, Md. Ali
Faizan, Md. Imam
Ahmed, Anwar
Almajhdi, Fahad N.
Hussain, Tajamul
Islam, Asimul
Parveen, Shama
author_facet Hamza, Abu
Samad, Abdus
Imam, Md. Ali
Faizan, Md. Imam
Ahmed, Anwar
Almajhdi, Fahad N.
Hussain, Tajamul
Islam, Asimul
Parveen, Shama
author_sort Hamza, Abu
collection PubMed
description The global burden of disease caused by a respiratory syncytial virus (RSV) is becoming more widely recognized in young children and adults. Heparan sulfate helps in attaching the virion through G protein with the host cell membrane. In this study, we examined the structural changes of ectodomain G protein (edG) in a wide pH range. The absorbance results revealed that protein maintains its tertiary structure at physiological and highly acidic and alkaline pH. However, visible aggregation of protein was observed in mild acidic pH. The intrinsic fluorescence study shows no significant change in the λ(max) except at pH 12.0. The ANS fluorescence of edG at pH 2.0 and 3.0 forms an acid-induced molten globule-like state. The denaturation transition curve monitored by fluorescence spectroscopy revealed that urea and GdmCl induced denaturation native (N) ↔ denatured (D) state follows a two-state process. The fluorescence quenching, molecular docking, and 50 ns simulation measurements suggested that heparan sulfate showed excellent binding affinity to edG. Our binding study provides a preliminary insight into the interaction of edG to the host cell membrane via heparan sulfate. This binding can be inhibited using experimental approaches at the molecular level leading to the prevention of effective host–pathogen interaction.
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spelling pubmed-86588832021-12-10 Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions Hamza, Abu Samad, Abdus Imam, Md. Ali Faizan, Md. Imam Ahmed, Anwar Almajhdi, Fahad N. Hussain, Tajamul Islam, Asimul Parveen, Shama Molecules Article The global burden of disease caused by a respiratory syncytial virus (RSV) is becoming more widely recognized in young children and adults. Heparan sulfate helps in attaching the virion through G protein with the host cell membrane. In this study, we examined the structural changes of ectodomain G protein (edG) in a wide pH range. The absorbance results revealed that protein maintains its tertiary structure at physiological and highly acidic and alkaline pH. However, visible aggregation of protein was observed in mild acidic pH. The intrinsic fluorescence study shows no significant change in the λ(max) except at pH 12.0. The ANS fluorescence of edG at pH 2.0 and 3.0 forms an acid-induced molten globule-like state. The denaturation transition curve monitored by fluorescence spectroscopy revealed that urea and GdmCl induced denaturation native (N) ↔ denatured (D) state follows a two-state process. The fluorescence quenching, molecular docking, and 50 ns simulation measurements suggested that heparan sulfate showed excellent binding affinity to edG. Our binding study provides a preliminary insight into the interaction of edG to the host cell membrane via heparan sulfate. This binding can be inhibited using experimental approaches at the molecular level leading to the prevention of effective host–pathogen interaction. MDPI 2021-12-06 /pmc/articles/PMC8658883/ /pubmed/34885979 http://dx.doi.org/10.3390/molecules26237398 Text en © 2021 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
Imam, Md. Ali
Faizan, Md. Imam
Ahmed, Anwar
Almajhdi, Fahad N.
Hussain, Tajamul
Islam, Asimul
Parveen, Shama
Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions
title Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions
title_full Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions
title_fullStr Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions
title_full_unstemmed Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions
title_short Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions
title_sort structural characterization of ectodomain g protein of respiratory syncytial virus and its interaction with heparan sulfate: multi-spectroscopic and in silico studies elucidating host-pathogen interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658883/
https://www.ncbi.nlm.nih.gov/pubmed/34885979
http://dx.doi.org/10.3390/molecules26237398
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