Conserved aromatic residues of the hepatitis B virus Precore propeptide are involved in a switch between distinct dimeric conformations and essential in the formation of heterocapsids

Abstract The Hepatitis B virus Precore protein, present in the secretory pathway as the HBeAg precursor, can associate in the cytoplasm with the Core protein to form heterocapsids, likely to favor viral persistence. Core and Precore proteins share their primary sequence except for ten additional ami...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2014-08, Vol.462, p.273-282
Main Authors: Duriez, Marion, Thouard, Anne, Bressanelli, Stéphane, Rossignol, Jean-Michel, Sitterlin, Delphine
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Cell Line
Conformational switch
Conserved Sequence
HBV expressing cell lines
Hepatitis B Core Antigens - genetics
Hepatitis B Core Antigens - metabolism
Hepatitis B virus
Hepatitis B virus - genetics
Hepatitis B virus - physiology
Hepatitis B virus Precore protein
Humans
Hydrophobic residues
Infectious Disease
Models, Molecular
Mutagenesis, Site-Directed
Mutant Proteins - genetics
Mutant Proteins - metabolism
Propeptide sequence
Protein Conformation
Protein Multimerization
Protein Precursors - genetics
Protein Precursors - metabolism
Viral heterocapsids
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Summary:Abstract The Hepatitis B virus Precore protein, present in the secretory pathway as the HBeAg precursor, can associate in the cytoplasm with the Core protein to form heterocapsids, likely to favor viral persistence. Core and Precore proteins share their primary sequence except for ten additional aminoacids at the N-terminus of Precore. To address the role of this propeptide sequence in the formation of Precore heterocapsids, we designed a Precore mutant in which the two propeptide tryptophans are replaced by glycines. This mutant retains the properties of the wild-type Precore, notably cell trafficking and ability to interact with Core. However, it is not incorporated into heterocapsids and forms stable dimers distinct from the labile HBe dimers and the presumably Core-like dimers assembled into heterocapsids. Our data highlights the essential role of Precore׳s propeptide in switching between different conformations for different functions and pinpoint the propeptide Tryptophan residues as central in these properties.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2014.06.013