Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly

Autores
Viso, Juan Francisco; Belelli, Patricia Gabriela; Machado, Matías Agustín; Gonzalez, Humberto; Pantano, Sergio; Amundarain, María Julia; Zamarreño, Fernando; Branda, Maria Marta; Guérin, Diego Marcelo Alejandro; Costabel, Marcelo Daniel
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in the capsid of small and non-enveloped icosahedral viruses. With this purpose we examine Triatoma Virus (TrV) as a case study. This virus has a stable capsid under highly acidic conditions but disassembles and releases the genome in alkaline environments. Our calculations range from a subtle sub-atomic proton interchange to the dismantling of a large-scale system representing several million of atoms. Our results provide structure-based explanations for the three roles played by the capsid to enable genome release. First, we observe, for the first time, the formation of a hydrophobic gate in the cavity along the five-fold axis of the wild-type virus capsid, which can be disrupted by an ion located in the pore. Second, the channel enables protons to permeate the capsid through a unidirectional Grotthuss-like mechanism, which is the most likely process through which the capsid senses pH. Finally, assuming that the proton leak promotes a charge imbalance in the interior of the capsid, we model an internal pressure that forces shell cracking using coarse-grained simulations. Although qualitatively, this last step could represent the mechanism of capsid opening that allows RNA release. All of our calculations are in agreement with current experimental data obtained using TrV and describe a cascade of events that could explain the destabilization and disassembly of similar icosahedral viruses.
Fil: Viso, Juan Francisco. Universidad Nacional del Sur; Argentina
Fil: Belelli, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Machado, Matías Agustín. Instituto Pasteur de Montevideo; Uruguay
Fil: González, Humberto. Instituto Pasteur de Montevideo; Uruguay
Fil: Pantano, Sergio. Instituto Pasteur de Montevideo; Uruguay
Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Branda, Maria Marta. Universidad Nacional del Sur; Argentina
Fil: Guérin, Diego Marcelo Alejandro. Universidad del País Vasco; España
Fil: Costabel, Marcelo Daniel. Universidad Nacional del Sur; Argentina
Materia
TrV
Molecular Dynamics
QM/MM
Proton channel
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/94750
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/94750
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassemblyViso, Juan FranciscoBelelli, Patricia GabrielaMachado, Matías AgustínGonzalez, HumbertoPantano, SergioAmundarain, María JuliaZamarreño, FernandoBranda, Maria MartaGuérin, Diego Marcelo AlejandroCostabel, Marcelo DanielTrVMolecular DynamicsQM/MMProton channelhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in the capsid of small and non-enveloped icosahedral viruses. With this purpose we examine Triatoma Virus (TrV) as a case study. This virus has a stable capsid under highly acidic conditions but disassembles and releases the genome in alkaline environments. Our calculations range from a subtle sub-atomic proton interchange to the dismantling of a large-scale system representing several million of atoms. Our results provide structure-based explanations for the three roles played by the capsid to enable genome release. First, we observe, for the first time, the formation of a hydrophobic gate in the cavity along the five-fold axis of the wild-type virus capsid, which can be disrupted by an ion located in the pore. Second, the channel enables protons to permeate the capsid through a unidirectional Grotthuss-like mechanism, which is the most likely process through which the capsid senses pH. Finally, assuming that the proton leak promotes a charge imbalance in the interior of the capsid, we model an internal pressure that forces shell cracking using coarse-grained simulations. Although qualitatively, this last step could represent the mechanism of capsid opening that allows RNA release. All of our calculations are in agreement with current experimental data obtained using TrV and describe a cascade of events that could explain the destabilization and disassembly of similar icosahedral viruses.Fil: Viso, Juan Francisco. Universidad Nacional del Sur; ArgentinaFil: Belelli, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Machado, Matías Agustín. Instituto Pasteur de Montevideo; UruguayFil: González, Humberto. Instituto Pasteur de Montevideo; UruguayFil: Pantano, Sergio. Instituto Pasteur de Montevideo; UruguayFil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Branda, Maria Marta. Universidad Nacional del Sur; ArgentinaFil: Guérin, Diego Marcelo Alejandro. Universidad del País Vasco; EspañaFil: Costabel, Marcelo Daniel. Universidad Nacional del Sur; ArgentinaPublic Library of Science2018-04-16info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/94750Viso, Juan Francisco; Belelli, Patricia Gabriela; Machado, Matías Agustín; Gonzalez, Humberto; Pantano, Sergio; et al.; Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly; Public Library of Science; Plos Computational Biology; 14; 4; 16-4-2018; 1-221553-734XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://dx.plos.org/10.1371/journal.pcbi.1006082info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pcbi.1006082info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:34:31Zoai:ri.conicet.gov.ar:11336/94750instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:34:31.512CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
title Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
spellingShingle Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
Viso, Juan Francisco
TrV
Molecular Dynamics
QM/MM
Proton channel
title_short Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
title_full Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
title_fullStr Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
title_full_unstemmed Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
title_sort Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
dc.creator.none.fl_str_mv Viso, Juan Francisco
Belelli, Patricia Gabriela
Machado, Matías Agustín
Gonzalez, Humberto
Pantano, Sergio
Amundarain, María Julia
Zamarreño, Fernando
Branda, Maria Marta
Guérin, Diego Marcelo Alejandro
Costabel, Marcelo Daniel
author Viso, Juan Francisco
author_facet Viso, Juan Francisco
Belelli, Patricia Gabriela
Machado, Matías Agustín
Gonzalez, Humberto
Pantano, Sergio
Amundarain, María Julia
Zamarreño, Fernando
Branda, Maria Marta
Guérin, Diego Marcelo Alejandro
Costabel, Marcelo Daniel
author_role author
author2 Belelli, Patricia Gabriela
Machado, Matías Agustín
Gonzalez, Humberto
Pantano, Sergio
Amundarain, María Julia
Zamarreño, Fernando
Branda, Maria Marta
Guérin, Diego Marcelo Alejandro
Costabel, Marcelo Daniel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TrV
Molecular Dynamics
QM/MM
Proton channel
topic TrV
Molecular Dynamics
QM/MM
Proton channel
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in the capsid of small and non-enveloped icosahedral viruses. With this purpose we examine Triatoma Virus (TrV) as a case study. This virus has a stable capsid under highly acidic conditions but disassembles and releases the genome in alkaline environments. Our calculations range from a subtle sub-atomic proton interchange to the dismantling of a large-scale system representing several million of atoms. Our results provide structure-based explanations for the three roles played by the capsid to enable genome release. First, we observe, for the first time, the formation of a hydrophobic gate in the cavity along the five-fold axis of the wild-type virus capsid, which can be disrupted by an ion located in the pore. Second, the channel enables protons to permeate the capsid through a unidirectional Grotthuss-like mechanism, which is the most likely process through which the capsid senses pH. Finally, assuming that the proton leak promotes a charge imbalance in the interior of the capsid, we model an internal pressure that forces shell cracking using coarse-grained simulations. Although qualitatively, this last step could represent the mechanism of capsid opening that allows RNA release. All of our calculations are in agreement with current experimental data obtained using TrV and describe a cascade of events that could explain the destabilization and disassembly of similar icosahedral viruses.
Fil: Viso, Juan Francisco. Universidad Nacional del Sur; Argentina
Fil: Belelli, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Machado, Matías Agustín. Instituto Pasteur de Montevideo; Uruguay
Fil: González, Humberto. Instituto Pasteur de Montevideo; Uruguay
Fil: Pantano, Sergio. Instituto Pasteur de Montevideo; Uruguay
Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Branda, Maria Marta. Universidad Nacional del Sur; Argentina
Fil: Guérin, Diego Marcelo Alejandro. Universidad del País Vasco; España
Fil: Costabel, Marcelo Daniel. Universidad Nacional del Sur; Argentina
description In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in the capsid of small and non-enveloped icosahedral viruses. With this purpose we examine Triatoma Virus (TrV) as a case study. This virus has a stable capsid under highly acidic conditions but disassembles and releases the genome in alkaline environments. Our calculations range from a subtle sub-atomic proton interchange to the dismantling of a large-scale system representing several million of atoms. Our results provide structure-based explanations for the three roles played by the capsid to enable genome release. First, we observe, for the first time, the formation of a hydrophobic gate in the cavity along the five-fold axis of the wild-type virus capsid, which can be disrupted by an ion located in the pore. Second, the channel enables protons to permeate the capsid through a unidirectional Grotthuss-like mechanism, which is the most likely process through which the capsid senses pH. Finally, assuming that the proton leak promotes a charge imbalance in the interior of the capsid, we model an internal pressure that forces shell cracking using coarse-grained simulations. Although qualitatively, this last step could represent the mechanism of capsid opening that allows RNA release. All of our calculations are in agreement with current experimental data obtained using TrV and describe a cascade of events that could explain the destabilization and disassembly of similar icosahedral viruses.
publishDate 2018
dc.date.none.fl_str_mv 2018-04-16
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/94750
Viso, Juan Francisco; Belelli, Patricia Gabriela; Machado, Matías Agustín; Gonzalez, Humberto; Pantano, Sergio; et al.; Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly; Public Library of Science; Plos Computational Biology; 14; 4; 16-4-2018; 1-22
1553-734X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/94750
identifier_str_mv Viso, Juan Francisco; Belelli, Patricia Gabriela; Machado, Matías Agustín; Gonzalez, Humberto; Pantano, Sergio; et al.; Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly; Public Library of Science; Plos Computational Biology; 14; 4; 16-4-2018; 1-22
1553-734X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://dx.plos.org/10.1371/journal.pcbi.1006082
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pcbi.1006082
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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