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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/94750
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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 |
_version_ |
1846083473556635648 |
score |
13.22299 |