Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein

Detalhes bibliográficos
Autor(a) principal: Souza, Theo Luiz Ferraz de
Data de Publicação: 2016
Outros Autores: Lima, Sheila Maria Barbosa de, Braga, Vanessa L. de Azevedo, Peabody, David S., Ferreira, Davis Fernandes, Bianconi, M. Lucia, Gomes, Andre Marco de Oliveira, Silva, Jerson Lima, Oliveira, Andréa Cheble de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/32417
Resumo: Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil.
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spelling Souza, Theo Luiz Ferraz deLima, Sheila Maria Barbosa deBraga, Vanessa L. de AzevedoPeabody, David S.Ferreira, Davis FernandesBianconi, M. LuciaGomes, Andre Marco de OliveiraSilva, Jerson LimaOliveira, Andréa Cheble de2019-04-08T19:29:00Z2019-04-08T19:29:00Z2016SOUZA, Theo Luiz Ferraz de et al. Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein. Peerj, Corte Madera, v. 4, n. 2670, p. 2-25, 2016.2167-8359https://www.arca.fiocruz.br/handle/icict/3241710.7717/peerj.2670engCharge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core proteininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.University of New Mexico. Department of Molecular Genetics and Microbiology and Cancer Research and Treatment Center. Albuquerque, USA.Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.BACKGROUND: Hepatitis C virus (HCV) core protein, in addition to its structural role to form the nucleocapsid assembly, plays a critical role in HCV pathogenesis by interfering in several cellular processes, including microRNA and mRNA homeostasis. The C-terminal truncated HCV core protein (C124) is intrinsically unstructured in solution and is able to interact with unspecific nucleic acids, in the micromolar range, and to assemble into nucleocapsid-like particles (NLPs) in vitro. The specificity and propensity of C124 to the assembly and its implications on HCV pathogenesis are not well understood. METHODS: Spectroscopic techniques, transmission electron microscopy and calorimetry were used to better understand the propensity of C124 to fold or to multimerize into NLPs when subjected to different conditions or in the presence of unspecific nucleic acids of equivalent size to cellular microRNAs. RESULTS: The structural analysis indicated that C124 has low propensity to self-folding. On the other hand, for the first time, we show that C124, in the absence of nucleic acids, multimerizes into empty NLPs when subjected to a pH close to its isoelectric point (pH ≈ 12), indicating that assembly is mainly driven by charge neutralization. Isothermal calorimetry data showed that the assembly of NLPs promoted by nucleic acids is enthalpy driven. Additionally, data obtained from fluorescence correlation spectroscopy show that C124, in nanomolar range, was able to interact and to sequester a large number of short unspecific nucleic acids into NLPs. DISCUSSION: Together, our data showed that the charge neutralization is the major factor for the nucleocapsid-like particles assembly from C-terminal truncated HCV core protein. This finding suggests that HCV core protein may physically interact with unspecific cellular polyanions, which may correspond to microRNAs and mRNAs in a host cell infected by HCV, triggering their confinement into infectious particles.Capsid assemblyCircular dichroismFluorescence spectroscopyHCV core proteinStructural biologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/32417/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALF151-peerj-04-2670.pdfapplication/pdf10071325https://www.arca.fiocruz.br/bitstream/icict/32417/2/F151-peerj-04-2670.pdf9a45a96fbd259bc84f1c0510c81483a2MD52TEXTF151-peerj-04-2670.pdf.txtF151-peerj-04-2670.pdf.txtExtracted texttext/plain69582https://www.arca.fiocruz.br/bitstream/icict/32417/3/F151-peerj-04-2670.pdf.txtf2f04757fd66bddccfd20183fc8b95bdMD53icict/324172019-04-09 02:01:14.681oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-04-09T05:01:14Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
title Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
spellingShingle Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
Souza, Theo Luiz Ferraz de
Capsid assembly
Circular dichroism
Fluorescence spectroscopy
HCV core protein
Structural biology
title_short Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
title_full Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
title_fullStr Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
title_full_unstemmed Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
title_sort Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein
author Souza, Theo Luiz Ferraz de
author_facet Souza, Theo Luiz Ferraz de
Lima, Sheila Maria Barbosa de
Braga, Vanessa L. de Azevedo
Peabody, David S.
Ferreira, Davis Fernandes
Bianconi, M. Lucia
Gomes, Andre Marco de Oliveira
Silva, Jerson Lima
Oliveira, Andréa Cheble de
author_role author
author2 Lima, Sheila Maria Barbosa de
Braga, Vanessa L. de Azevedo
Peabody, David S.
Ferreira, Davis Fernandes
Bianconi, M. Lucia
Gomes, Andre Marco de Oliveira
Silva, Jerson Lima
Oliveira, Andréa Cheble de
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Souza, Theo Luiz Ferraz de
Lima, Sheila Maria Barbosa de
Braga, Vanessa L. de Azevedo
Peabody, David S.
Ferreira, Davis Fernandes
Bianconi, M. Lucia
Gomes, Andre Marco de Oliveira
Silva, Jerson Lima
Oliveira, Andréa Cheble de
dc.subject.en.pt_BR.fl_str_mv Capsid assembly
Circular dichroism
Fluorescence spectroscopy
HCV core protein
Structural biology
topic Capsid assembly
Circular dichroism
Fluorescence spectroscopy
HCV core protein
Structural biology
description Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil.
publishDate 2016
dc.date.issued.fl_str_mv 2016
dc.date.accessioned.fl_str_mv 2019-04-08T19:29:00Z
dc.date.available.fl_str_mv 2019-04-08T19:29:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SOUZA, Theo Luiz Ferraz de et al. Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein. Peerj, Corte Madera, v. 4, n. 2670, p. 2-25, 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/32417
dc.identifier.issn.pt_BR.fl_str_mv 2167-8359
dc.identifier.doi.none.fl_str_mv 10.7717/peerj.2670
identifier_str_mv SOUZA, Theo Luiz Ferraz de et al. Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein. Peerj, Corte Madera, v. 4, n. 2670, p. 2-25, 2016.
2167-8359
10.7717/peerj.2670
url https://www.arca.fiocruz.br/handle/icict/32417
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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