title: Role for calnexin and N-linked glycosylation in the assembly and secretion of hepatitis B virus middle envelope protein particles.
abstract: Unlike those of the S and the L envelope proteins, the functional role of the related M protein in the life cycle of the hepatitis B virus (HBV) is less understood. We now demonstrate that a single N glycan, specific for M, is required for efficient secretion of M empty envelope particles. Moreover, this glycan mediates specific association of M with the chaperone calnexin. Conversely, the N glycan, common to all three envelope proteins, is involved neither in calnexin binding nor in subviral particle release. As proper folding and trafficking of M need the assistance of the chaperone, the glycan-dependent association of M with calnexin may thus play a crucial role in the assembly of HBV. Beyond being modified by N glycosylation, M is modified by O glycosylation occurring within its amino acid sequence at positions 27 to 47. The O glycans, however, were found to be dispensable for secretion of M but may rather support viral infectivity. Surprisingly, nonglycosylated M localizes exclusively to the cytosol, either for degradation or for a yet-unknown function.
authors.affiliation: Institute for Medical Microbiology and Hygiene, Johannes Gutenberg-Universität Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Werr
authors.forename: R
authors.initials: R
authors.lastname: Prange
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000502:physiology*; D037281:Calnexin; D003600:Cytosol / Q000378:metabolism; D006031:Glycosylation; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D009838:Oligodeoxyribonucleotides; D014759:Viral Envelope Proteins; D037281:Calnexin