Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/23429 |
Resumo: | © 2014 American Chemical Society |
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Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition© 2014 American Chemical SocietyDengue virus (DENV) infection affects millions of people and is becoming a major global disease for which there is no specific available treatment. pep14-23 is a recently designed peptide, based on a conserved segment of DENV capsid (C) protein. It inhibits the interaction of DENV C with host intracellular lipid droplets (LDs), which is crucial for viral replication. Combining bioinformatics and biophysics, here, we analyzed pep14-23 structure and ability to bind different phospholipids, relating that information with the full-length DENV C. We show that pep14-23 acquires α-helical conformation upon binding to negatively charged phospholipid membranes, displaying an asymmetric charge distribution structural arrangement. Structure prediction for the N-terminal segment reveals four viable homodimer orientations that alternatively shield or expose the DENV C hydrophobic pocket. Taken together, these findings suggest a new biological role for the disordered Nterminal region, which may function as an autoinhibitory domain mediating DENV C interaction with its biological targets. The results fit with our current understanding of DENV C and pep14-23 structure and function, paving the way for similar approaches to understanding disordered proteins and improved peptidomimetics drug development strategies against DENV and similar Flavivirus infections.The authors thank T. Freitas (IMM, FMUL) for technical assistance. This work was supported by Fundação para a Ciência e Tecnologia Ministério da Educação e Ciência (FCT-MEC, Portugal) projects PTDC/QUI-BIQ/112929/2009 and PTDC/SAU-ENB/117013/2010, Calouste Gulbenkian Foundation (FCG, Portugal) project Science Frontiers Research Prize 2010, European Union project FP7-IRSES MEMPEPACROSS, Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq, Brazil, grant numbers 471239/2012-7 and 306669/2013-7) and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil, grant numbers E-26/102.919/2011 and E-26/110.636/2012). A.F.F. and A.H. also acknowledge FCT-MEC fellowships SFRH/BD/77609/2011 and SFRH/BPD/72037/2010, respectively. I.C.M. acknowledges consecutive funding from the FCT-MEC fellowship SFRH/BPD/74287/2010 and the Program “Investigador FCT” (IF/00772/2013 Research Contract).American Chemical SocietyRepositório da Universidade de LisboaFaustino, André F.Guerra, Gabriela M.Huber, Roland G.Hollmann, AxelDomingues, Marco M.Barbosa, Glauce M.Enguita, Francisco J.Bond, Peter J.Castanho, Miguel A. R. B.Poian, Andrea T. daAlmeida, Fabio C. L.2016-04-18T15:48:47Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/23429engACS Chem. Biol. 2015, 10, 517−5261554-892910.1021/cb500640tmetadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:10:45Zoai:repositorio.ul.pt:10451/23429Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:40:30.032927Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition |
| title |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition |
| spellingShingle |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition Faustino, André F. |
| title_short |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition |
| title_full |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition |
| title_fullStr |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition |
| title_full_unstemmed |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition |
| title_sort |
Understanding dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition |
| author |
Faustino, André F. |
| author_facet |
Faustino, André F. Guerra, Gabriela M. Huber, Roland G. Hollmann, Axel Domingues, Marco M. Barbosa, Glauce M. Enguita, Francisco J. Bond, Peter J. Castanho, Miguel A. R. B. Poian, Andrea T. da Almeida, Fabio C. L. |
| author_role |
author |
| author2 |
Guerra, Gabriela M. Huber, Roland G. Hollmann, Axel Domingues, Marco M. Barbosa, Glauce M. Enguita, Francisco J. Bond, Peter J. Castanho, Miguel A. R. B. Poian, Andrea T. da Almeida, Fabio C. L. |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Faustino, André F. Guerra, Gabriela M. Huber, Roland G. Hollmann, Axel Domingues, Marco M. Barbosa, Glauce M. Enguita, Francisco J. Bond, Peter J. Castanho, Miguel A. R. B. Poian, Andrea T. da Almeida, Fabio C. L. |
| description |
© 2014 American Chemical Society |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2016-04-18T15:48:47Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/23429 |
| url |
http://hdl.handle.net/10451/23429 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
ACS Chem. Biol. 2015, 10, 517−526 1554-8929 10.1021/cb500640t |
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metadata only access info:eu-repo/semantics/openAccess |
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metadata only access |
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openAccess |
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application/pdf |
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American Chemical Society |
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American Chemical Society |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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