title: 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 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.
authors.affiliation: Université Versailles St-Quentin, EA 4589 / EPHE, Laboratoire de Génétique et Biologie Cellulaire, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France. Electronic address: marion.duriez@inserm.fr.
authors.forename: Marion
authors.initials: M
authors.lastname: Duriez
authors.affiliation: Université Versailles St-Quentin, EA 4589 / EPHE, Laboratoire de Génétique et Biologie Cellulaire, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France. Electronic address: anne.thouard@inserm.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Thouard
authors.affiliation: Université Versailles St-Quentin, EA 4589 / EPHE, Laboratoire de Génétique et Biologie Cellulaire, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France. Electronic address: stephane.bressanelli@vms.cnrs-gif.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bressanelli
authors.affiliation: Université Versailles St-Quentin, EA 4589 / EPHE, Laboratoire de Génétique et Biologie Cellulaire, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France. Electronic address: Jean-Michel.Rossignol@legs.cnrs-gif.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rossignol
authors.affiliation: Université Versailles St-Quentin, EA 4589 / EPHE, Laboratoire de Génétique et Biologie Cellulaire, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France. Electronic address: delphine.sitterlin@uvsq.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Sitterlin
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D017124:Conserved Sequence; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D055503:Protein Multimerization; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006512:Hepatitis B Core Antigens; D050505:Mutant Proteins; D011498:Protein Precursors
keywords: Conformational switch; HBV expressing cell lines; Hepatitis B virus Precore protein; Hydrophobic residues; Propeptide sequence; Viral heterocapsids