Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen

Norovirus infectivity, which causes norovirus-induced gastroenteritis,depends on the interaction between capsid protein VP1 of the virus and hostcell HGBA receptors that tailor the cell membrane surface. The interactionresults in VP1-HGBA complex formation prior to infection. The details of thisinte...

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Main Authors: Abdulkadir Kocak, Muslum Yildiz
Format: Article
Language:English
Published: Sakarya University 2019-12-01
Series:Sakarya Üniversitesi Fen Bilimleri Enstitüsü Dergisi
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Online Access:https://dergipark.org.tr/tr/download/article-file/793007
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author Abdulkadir Kocak
Muslum Yildiz
author_facet Abdulkadir Kocak
Muslum Yildiz
author_sort Abdulkadir Kocak
collection DOAJ
description Norovirus infectivity, which causes norovirus-induced gastroenteritis,depends on the interaction between capsid protein VP1 of the virus and hostcell HGBA receptors that tailor the cell membrane surface. The interactionresults in VP1-HGBA complex formation prior to infection. The details of thisinteraction have been provided by x-ray structures of HGBA-VP1 complexes, butthe dynamic nature of this interaction is not fully uncovered. Therefore, thedynamics that drive the formation of VP1-HGBA complex, which is crucial fordeveloping new therapeutic approaches to find a cure for gastroenteritisdisease, need to be elucidated. Here, we computationally analyzed the wild typeVP1 capsid protein in complex with A-type HGBA antigen to unravel interactionsthat are important for virus to enter inside the host cell during infection. Wehave found that the ligand binding causes a fluctuation in a distant loop whichresides in the interface of capsid building blocks, VP proteins. Thisfluctuation leads an instability in capsid particle that may be an indicationfor virus uncoating mechanism during the cell penetration.
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spelling doaj-art-ecc37d53e54c4bdb869b96d839155ca02025-08-20T02:31:51ZengSakarya UniversitySakarya Üniversitesi Fen Bilimleri Enstitüsü Dergisi2147-835X2019-12-012361056106510.16984/saufenbilder.52543028Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type AntigenAbdulkadir Kocakhttps://orcid.org/0000-0001-6891-6929Muslum Yildizhttps://orcid.org/0000-0001-8396-1461Norovirus infectivity, which causes norovirus-induced gastroenteritis,depends on the interaction between capsid protein VP1 of the virus and hostcell HGBA receptors that tailor the cell membrane surface. The interactionresults in VP1-HGBA complex formation prior to infection. The details of thisinteraction have been provided by x-ray structures of HGBA-VP1 complexes, butthe dynamic nature of this interaction is not fully uncovered. Therefore, thedynamics that drive the formation of VP1-HGBA complex, which is crucial fordeveloping new therapeutic approaches to find a cure for gastroenteritisdisease, need to be elucidated. Here, we computationally analyzed the wild typeVP1 capsid protein in complex with A-type HGBA antigen to unravel interactionsthat are important for virus to enter inside the host cell during infection. Wehave found that the ligand binding causes a fluctuation in a distant loop whichresides in the interface of capsid building blocks, VP proteins. Thisfluctuation leads an instability in capsid particle that may be an indicationfor virus uncoating mechanism during the cell penetration.https://dergipark.org.tr/tr/download/article-file/793007norovirustherapeutic antibodyhbga blockagemolecular dynamics
spellingShingle Abdulkadir Kocak
Muslum Yildiz
Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen
Sakarya Üniversitesi Fen Bilimleri Enstitüsü Dergisi
norovirus
therapeutic antibody
hbga blockage
molecular dynamics
title Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen
title_full Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen
title_fullStr Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen
title_full_unstemmed Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen
title_short Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen
title_sort computational interrogation of the human norovirus host cell interactions facilitated by a type antigen
topic norovirus
therapeutic antibody
hbga blockage
molecular dynamics
url https://dergipark.org.tr/tr/download/article-file/793007
work_keys_str_mv AT abdulkadirkocak computationalinterrogationofthehumannorovirushostcellinteractionsfacilitatedbyatypeantigen
AT muslumyildiz computationalinterrogationofthehumannorovirushostcellinteractionsfacilitatedbyatypeantigen