De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold

Detalhes bibliográficos
Autor(a) principal: Viana, Isabelle Freire Tabosa
Data de Publicação: 2013
Outros Autores: Soares, Thereza A., Lima, Lucianna F. O., Marques, Ernesto T. A., Krieger, Marco Aurélio, Dhalia, Rafael, Lins, Roberto D.
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/15826
Resumo: FACEPE, NanoBiotec-BR/CAPES, CNPq, INCT-INAMI, nBioNet, Oswaldo Cruz Foundation.
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spelling Viana, Isabelle Freire TabosaSoares, Thereza A.Lima, Lucianna F. O.Marques, Ernesto T. A.Krieger, Marco AurélioDhalia, RafaelLins, Roberto D.2016-09-16T17:40:03Z2016-09-16T17:40:03Z2013VIANA, Isabelle Freire Tabosa et al. De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold. RSC Advances, p. 11790–11800, 2013.2046-2069https://www.arca.fiocruz.br/handle/icict/1582610.1039/c3ra41562gFACEPE, NanoBiotec-BR/CAPES, CNPq, INCT-INAMI, nBioNet, Oswaldo Cruz Foundation.Federal University of Pernambuco. Department of Fundamental Chemistry. Recife, PE, Brazil.University of Pittsburg. Department of Infectious Diseases and Microbiology. Pittsburgh, USA.Oswaldo Cruz Foundation. Carlos Chagas Institute. Curitiba, PR, Brazil.Oswaldo Cruz Foundation. Aggeu Magalhães Research Center. Recife, PE, Brazil.Epitope exposure strategies often fail due to high conformational instability, resulting in loss of native conformation and fast degradation. Protein scaffolding, where a structural element of an antigen protein is transplanted into a scaffold acceptor protein, has been employed as an alternative solution. However, while this approach aims to preserve the epitope structure, it frequently results in unstable chimeric scaffolds. To overcome this issue, we employed a novel computational approach to rationally engineer conformational antigens into a highly stable scaffold protein. This strategy is showcased to display conformational HIV-1 gp41-based epitopes in their native structure. From HIV-1 antigen sequence databases, we have identified short sequences with the most probable antibody-recognizable regions. These sequences were inserted into or replaced regions of the original Top7 protein with analogous secondary structure assignment. Molecular dynamics simulations were used to characterize the protein stability and structural dynamic of the chimeric proteins, leading to a selection of promising candidates whose immunogenic epitopes are suitably exposed for antibody recognition. These computer-designed recombinant proteins were produced in bacteria using codon optimized DNA sequences and their diagnostic performance was assessed by liquid microarray against a human cohort of 47 sera samples. Our results show that the Top7 protein is a suitable scaffold to provide the required structural stability to predetermined target shapes and sequences, allowing the potential use of the chimeric proteins as antigens for specific antibody recognition and/or stimulation of immune response.porMike D WardDe novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffoldinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleProtein scaffoldingDesignHIV-1Epitopeinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83074https://www.arca.fiocruz.br/bitstream/icict/15826/1/license.txt0271fb68963c017aa933c7aff60379f4MD51ORIGINALDe novo design.pdfDe novo design.pdfapplication/pdf980251https://www.arca.fiocruz.br/bitstream/icict/15826/2/De%20novo%20design.pdfcd50fe658dcec7c21d19b8fd628a792eMD52TEXTDe novo 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dc.title.pt_BR.fl_str_mv De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
title De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
spellingShingle De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
Viana, Isabelle Freire Tabosa
Protein scaffolding
Design
HIV-1
Epitope
title_short De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
title_full De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
title_fullStr De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
title_full_unstemmed De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
title_sort De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold
author Viana, Isabelle Freire Tabosa
author_facet Viana, Isabelle Freire Tabosa
Soares, Thereza A.
Lima, Lucianna F. O.
Marques, Ernesto T. A.
Krieger, Marco Aurélio
Dhalia, Rafael
Lins, Roberto D.
author_role author
author2 Soares, Thereza A.
Lima, Lucianna F. O.
Marques, Ernesto T. A.
Krieger, Marco Aurélio
Dhalia, Rafael
Lins, Roberto D.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Viana, Isabelle Freire Tabosa
Soares, Thereza A.
Lima, Lucianna F. O.
Marques, Ernesto T. A.
Krieger, Marco Aurélio
Dhalia, Rafael
Lins, Roberto D.
dc.subject.en.pt_BR.fl_str_mv Protein scaffolding
Design
HIV-1
Epitope
topic Protein scaffolding
Design
HIV-1
Epitope
description FACEPE, NanoBiotec-BR/CAPES, CNPq, INCT-INAMI, nBioNet, Oswaldo Cruz Foundation.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-09-16T17:40:03Z
dc.date.available.fl_str_mv 2016-09-16T17:40:03Z
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 VIANA, Isabelle Freire Tabosa et al. De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold. RSC Advances, p. 11790–11800, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/15826
dc.identifier.issn.pt_BR.fl_str_mv 2046-2069
dc.identifier.doi.pt_BR.fl_str_mv 10.1039/c3ra41562g
identifier_str_mv VIANA, Isabelle Freire Tabosa et al. De novo design of immunoreactive conformationspecific HIV-1 epitopes based on Top7 scaffold. RSC Advances, p. 11790–11800, 2013.
2046-2069
10.1039/c3ra41562g
url https://www.arca.fiocruz.br/handle/icict/15826
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Mike D Ward
publisher.none.fl_str_mv Mike D Ward
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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instacron_str FIOCRUZ
institution FIOCRUZ
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