Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i>
Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core....
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doaj-eeea0a8ac53744b8aa659de4c03aa01d2020-11-25T01:57:18ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-08-012016387010.3390/ijms20163870ijms20163870Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i>André F. Faustino0Ana S. Martins1Nina Karguth2Vanessa Artilheiro3Francisco J. Enguita4Joana C. Ricardo5Nuno C. Santos6Ivo C. Martins7Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, PortugalCentro de Química-Física Molecular, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, PortugalDengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems. The capsid is a homodimeric protein that contains a disordered N-terminal region, an intermediate flexible fold section and a very stable conserved fold region. Since a better understanding of its structure can give light into its biological activity, here, first, we compared and analyzed relevant mosquito-borne <i>Flavivirus</i> capsid protein sequences and their predicted structures. Then, we studied the alternative conformations enabled by the N-terminal region. Finally, using dengue virus capsid protein as main model, we correlated the protein size, thermal stability and function with its structure/dynamics features. The findings suggest that the capsid protein interaction with host lipid systems leads to minor allosteric changes that may modulate the specific binding of the protein to the viral RNA. Such mechanism can be targeted in future drug development strategies, namely by using improved versions of pep14-23, a dengue virus capsid protein peptide inhibitor, previously developed by us. Such knowledge can yield promising advances against Zika, dengue and closely related <i>Flavivirus</i>.https://www.mdpi.com/1422-0067/20/16/3870Dengue virus (DENV)capsid protein (C protein)<i>Flavivirus</i>intrinsically disordered protein (IDP)protein–RNA interactionsprotein–host lipid systems interactioncircular dichroismtime-resolved fluorescence anisotropy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
André F. Faustino Ana S. Martins Nina Karguth Vanessa Artilheiro Francisco J. Enguita Joana C. Ricardo Nuno C. Santos Ivo C. Martins |
spellingShingle |
André F. Faustino Ana S. Martins Nina Karguth Vanessa Artilheiro Francisco J. Enguita Joana C. Ricardo Nuno C. Santos Ivo C. Martins Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i> International Journal of Molecular Sciences Dengue virus (DENV) capsid protein (C protein) <i>Flavivirus</i> intrinsically disordered protein (IDP) protein–RNA interactions protein–host lipid systems interaction circular dichroism time-resolved fluorescence anisotropy |
author_facet |
André F. Faustino Ana S. Martins Nina Karguth Vanessa Artilheiro Francisco J. Enguita Joana C. Ricardo Nuno C. Santos Ivo C. Martins |
author_sort |
André F. Faustino |
title |
Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i> |
title_short |
Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i> |
title_full |
Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i> |
title_fullStr |
Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i> |
title_full_unstemmed |
Structural and Functional Properties of the Capsid Protein of Dengue and Related <i>Flavivirus</i> |
title_sort |
structural and functional properties of the capsid protein of dengue and related <i>flavivirus</i> |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-08-01 |
description |
Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems. The capsid is a homodimeric protein that contains a disordered N-terminal region, an intermediate flexible fold section and a very stable conserved fold region. Since a better understanding of its structure can give light into its biological activity, here, first, we compared and analyzed relevant mosquito-borne <i>Flavivirus</i> capsid protein sequences and their predicted structures. Then, we studied the alternative conformations enabled by the N-terminal region. Finally, using dengue virus capsid protein as main model, we correlated the protein size, thermal stability and function with its structure/dynamics features. The findings suggest that the capsid protein interaction with host lipid systems leads to minor allosteric changes that may modulate the specific binding of the protein to the viral RNA. Such mechanism can be targeted in future drug development strategies, namely by using improved versions of pep14-23, a dengue virus capsid protein peptide inhibitor, previously developed by us. Such knowledge can yield promising advances against Zika, dengue and closely related <i>Flavivirus</i>. |
topic |
Dengue virus (DENV) capsid protein (C protein) <i>Flavivirus</i> intrinsically disordered protein (IDP) protein–RNA interactions protein–host lipid systems interaction circular dichroism time-resolved fluorescence anisotropy |
url |
https://www.mdpi.com/1422-0067/20/16/3870 |
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