Assessment of determinants affecting the dual topology of hepadnaviral large envelope proteins.
For functional diversity, the large (L) envelope protein of hepatitis B virus (HBV) acquires a dual transmembrane topology via co-translational membrane integration of the S region and partial post-translational translocation of the preS subdomain. Because each process requires the second transmembrane segment (TM2), we explored the action of this determinant by using protease protection analysis of mutant L proteins. We demonstrated that neither the disruption of a leucine zipper-like motif by multiple alanine substitutions nor the flanking charges of TM2 affected the topological reorientation of L. The dispensability of both putative subunit interaction modules argues against a link between preS post-translocation and envelope assembly. Phenotypic mixing experiments revealed that the preS and S protein domains of the related duck HBV L polypeptide failed to substitute functionally for the topogenic elements of HBV in directing the correct L topogenesis, implicating different translocation mechanisms used by the two hepadnavirus genera.
Lambert
Carsten
C
Department of Medical Microbiology and Hygiene, University of Mainz, Augustusplatz, D-55101 Mainz, Germany.
Mann
Sylvia
S
Department of Medical Microbiology and Hygiene, University of Mainz, Augustusplatz, D-55101 Mainz, Germany.
Prange
Reinhild
R
Department of Medical Microbiology and Hygiene, University of Mainz, Augustusplatz, D-55101 Mainz, Germany.
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins