Mammalian BiP controls posttranslational ER translocation of the hepatitis B virus large envelope protein.
The hepatitis B virus L protein forms a dual topology in the endoplasmic reticulum (ER) via a process involving cotranslational membrane integration and subsequent posttranslational translocation of its preS subdomain. Here, we show that preS posttranslocation depends on the action of the ER chaperone BiP. To modulate the in vivo BiP activity, we designed an approach based on overexpressing its positive and negative regulators, ER-localized DnaJ-domain containing protein 4 (ERdj4) and BiP-associated protein (BAP), respectively. The feasibility of this approach was confirmed by demonstrating that BAP, but not ERdj4, destabilizes the L/BiP complex. Overexpressing BAP or ERdj4 inhibits preS posttranslocation as does the reduction of ATP levels. These results hint to a new role of BiP in guiding posttranslational polypeptide import into the mammalian ER.
Awe
Karin
K
Department of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, D-55101 Mainz, Germany.
Lambert
Carsten
C
Prange
Reinhild
R
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
C478021:DNAJB9 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C096362:L protein, hepatitis B virus; D008565:Membrane Proteins; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins; D000255:Adenosine Triphosphate