Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.

The Hepatitis B Virus (HBV) double-stranded DNA genome is reverse transcribed from its RNA pregenome (pgRNA) within the virus core (or capsid). Phosphorylation of the arginine-rich carboxy-terminal domain (CTD) of the HBV capsid protein (Cp183) is essential for pgRNA encapsidation and reverse transc...

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Autores principales:	Joseph C-Y Wang, Mary S Dhason, Adam Zlotnick
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2b2a4945ecf64abfb10be450a4fb6d60
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spelling	oai:doaj.org-article:2b2a4945ecf64abfb10be450a4fb6d602021-11-18T06:03:57ZStructural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.1553-73661553-737410.1371/journal.ppat.1002919https://doaj.org/article/2b2a4945ecf64abfb10be450a4fb6d602012-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028319/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The Hepatitis B Virus (HBV) double-stranded DNA genome is reverse transcribed from its RNA pregenome (pgRNA) within the virus core (or capsid). Phosphorylation of the arginine-rich carboxy-terminal domain (CTD) of the HBV capsid protein (Cp183) is essential for pgRNA encapsidation and reverse transcription. However, the structure of the CTD remains poorly defined. Here we report sub-nanometer resolution cryo-EM structures of in vitro assembled empty and pgRNA-filled Cp183 capsids in unphosphorylated and phosphorylation-mimic states. In empty capsids, we found unexpected evidence of surface accessible CTD density partially occluding pores in the capsid surface. We also observed that CTD organization changed substantively as a function of phosphorylation. In RNA-filled capsids, unphosphorylated CTDs favored thick ropes of RNA, while the phosphorylation-mimic favored a mesh of thin, high-density strands suggestive of single stranded RNA. These results demonstrate that the CTD can regulate nucleic acid structure, supporting the hypothesis that the HBV capsid has a functional role as a nucleic acid chaperone.Joseph C-Y WangMary S DhasonAdam ZlotnickPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 9, p e1002919 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Joseph C-Y Wang Mary S Dhason Adam Zlotnick Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.
description	The Hepatitis B Virus (HBV) double-stranded DNA genome is reverse transcribed from its RNA pregenome (pgRNA) within the virus core (or capsid). Phosphorylation of the arginine-rich carboxy-terminal domain (CTD) of the HBV capsid protein (Cp183) is essential for pgRNA encapsidation and reverse transcription. However, the structure of the CTD remains poorly defined. Here we report sub-nanometer resolution cryo-EM structures of in vitro assembled empty and pgRNA-filled Cp183 capsids in unphosphorylated and phosphorylation-mimic states. In empty capsids, we found unexpected evidence of surface accessible CTD density partially occluding pores in the capsid surface. We also observed that CTD organization changed substantively as a function of phosphorylation. In RNA-filled capsids, unphosphorylated CTDs favored thick ropes of RNA, while the phosphorylation-mimic favored a mesh of thin, high-density strands suggestive of single stranded RNA. These results demonstrate that the CTD can regulate nucleic acid structure, supporting the hypothesis that the HBV capsid has a functional role as a nucleic acid chaperone.
format	article
author	Joseph C-Y Wang Mary S Dhason Adam Zlotnick
author_facet	Joseph C-Y Wang Mary S Dhason Adam Zlotnick
author_sort	Joseph C-Y Wang
title	Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.
title_short	Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.
title_full	Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.
title_fullStr	Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.
title_full_unstemmed	Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.
title_sort	structural organization of pregenomic rna and the carboxy-terminal domain of the capsid protein of hepatitis b virus.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2b2a4945ecf64abfb10be450a4fb6d60
work_keys_str_mv	AT josephcywang structuralorganizationofpregenomicrnaandthecarboxyterminaldomainofthecapsidproteinofhepatitisbvirus AT marysdhason structuralorganizationofpregenomicrnaandthecarboxyterminaldomainofthecapsidproteinofhepatitisbvirus AT adamzlotnick structuralorganizationofpregenomicrnaandthecarboxyterminaldomainofthecapsidproteinofhepatitisbvirus
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Structural organization of pregenomic RNA and the carboxy-terminal domain of the capsid protein of hepatitis B virus.

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