A metastable form of the large envelope protein of duck hepatitis B virus: low-pH release results in a transition to a hydrophobic, potentially fusogenic conformation.
We have examined the structure and fusion potential of the duck hepatitis B virus (DHBV) envelope proteins by treating subviral particles with deforming agents known to release envelope proteins of viruses from a metastable to a fusion-active state. Exposure of DHBV particles to low pH triggered a major structural change in the large envelope protein (L), resulting in exposure of trypsin sites within its S domain but without affecting the same region in the small surface protein (S) subunits. This conformational change was associated with increased hydrophobicity of the particle surface, most likely arising from surface exposure of the hydrophobic first transmembrane domain (TM1). In the hydrophobic conformation, DHBV particles were able to bind to liposomes and intact cells, while in their absence these particles aggregated, resulting in viral inactivation. These results suggests that some L molecules are in a spring-loaded metastable state which, when released, exposes a previously hidden hydrophobic domain, a transition potentially representing the fusion-active state of the envelope.
Grgacic
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Macfarlane Burnet Centre for Medical Research and Australian Centre for Hepatitis Virology, Fairfield 3078, Victoria, Australia. grgacic@burnet.edu.au
Schaller
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H
D000818:Animals; D001665:Binding Sites; D004229:Dithiothreitol / Q000494:pharmacology; D004372:Ducks; D006361:Heating; D015611:Hepatitis B Virus, Duck / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000378:metabolism; D011487:Protein Conformation; D014357:Trypsin / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D014771:Virion / Q000378:metabolism
C096362:L protein, hepatitis B virus; D008081:Liposomes; C077433:Pre-S protein, Duck hepatitis B virus; D014759:Viral Envelope Proteins; D014357:Trypsin; D004229:Dithiothreitol