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Allosteric conformational changes of human HBV core protein transform its assembly

Hepatitis B Virus core protein (HBc) has multiple roles in the viral lifecycle: viral assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions. HBc displays assembly polymorphism - it can assemble into icosahedral capsid and aberrant non-capsid structures. It...

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Autores principales: Liu, Chuang, Fan, Guizhen, Wang, Zhao, Chen, Hong-Song, Yin, Chang-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431180/
https://www.ncbi.nlm.nih.gov/pubmed/28469174
http://dx.doi.org/10.1038/s41598-017-01568-9
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author Liu, Chuang
Fan, Guizhen
Wang, Zhao
Chen, Hong-Song
Yin, Chang-Cheng
author_facet Liu, Chuang
Fan, Guizhen
Wang, Zhao
Chen, Hong-Song
Yin, Chang-Cheng
author_sort Liu, Chuang
collection PubMed
description Hepatitis B Virus core protein (HBc) has multiple roles in the viral lifecycle: viral assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions. HBc displays assembly polymorphism - it can assemble into icosahedral capsid and aberrant non-capsid structures. It has been hypothesized that the assembly polymorphism is due to allosteric conformational changes of HBc dimer, the smallest assembly unit, however, the mechanism governing the polymorphic assembly of the HBc dimer is still elusive. By using the experimental antiviral drug BAY 41-4109, we successfully transformed the HBc assembly from icosahedral capsid to helical tube. Structural analyses of HBc dimers from helical tubes, T = 4 icosahedral capsid, and sheet-like HBc ensemble revealed differences within the inter-dimer interface. Disruption of the HBc inter-dimer interface may likely promote the various assembly forms of HBc. Our work provides new structural insights into the HBV assembly mechanism and strategic guide for anti-HBV drug design.
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spelling pubmed-54311802017-05-16 Allosteric conformational changes of human HBV core protein transform its assembly Liu, Chuang Fan, Guizhen Wang, Zhao Chen, Hong-Song Yin, Chang-Cheng Sci Rep Article Hepatitis B Virus core protein (HBc) has multiple roles in the viral lifecycle: viral assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions. HBc displays assembly polymorphism - it can assemble into icosahedral capsid and aberrant non-capsid structures. It has been hypothesized that the assembly polymorphism is due to allosteric conformational changes of HBc dimer, the smallest assembly unit, however, the mechanism governing the polymorphic assembly of the HBc dimer is still elusive. By using the experimental antiviral drug BAY 41-4109, we successfully transformed the HBc assembly from icosahedral capsid to helical tube. Structural analyses of HBc dimers from helical tubes, T = 4 icosahedral capsid, and sheet-like HBc ensemble revealed differences within the inter-dimer interface. Disruption of the HBc inter-dimer interface may likely promote the various assembly forms of HBc. Our work provides new structural insights into the HBV assembly mechanism and strategic guide for anti-HBV drug design. Nature Publishing Group UK 2017-05-03 /pmc/articles/PMC5431180/ /pubmed/28469174 http://dx.doi.org/10.1038/s41598-017-01568-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Chuang
Fan, Guizhen
Wang, Zhao
Chen, Hong-Song
Yin, Chang-Cheng
Allosteric conformational changes of human HBV core protein transform its assembly
title Allosteric conformational changes of human HBV core protein transform its assembly
title_full Allosteric conformational changes of human HBV core protein transform its assembly
title_fullStr Allosteric conformational changes of human HBV core protein transform its assembly
title_full_unstemmed Allosteric conformational changes of human HBV core protein transform its assembly
title_short Allosteric conformational changes of human HBV core protein transform its assembly
title_sort allosteric conformational changes of human hbv core protein transform its assembly
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431180/
https://www.ncbi.nlm.nih.gov/pubmed/28469174
http://dx.doi.org/10.1038/s41598-017-01568-9
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