This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Beck, J.
Right arrow Articles by Nassal, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Beck, J.
Right arrow Articles by Nassal, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 1998, p. 6265-6272, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Formation of a Functional Hepatitis B Virus Replication Initiation Complex Involves a Major Structural Alteration in the RNA Template

Jürgen Beck and Michael Nassal*

Department of Internal Medicine II/Molecular Biology, University Hospital Freiburg, D-79106 Freiburg, Germany

Received 16 March 1998/Returned for modification 28 April 1998/Accepted 27 July 1998

The DNA genome of a hepatitis B virus is generated by reverse transcription of the RNA pregenome. Replication initiation does not involve a nucleic acid primer; instead, the hepadnavirus P protein binds to the structured RNA encapsidation signal varepsilon , from which it copies a short DNA primer that becomes covalently linked to the enzyme. Using in vitro-translated duck hepatitis B virus (DHBV) P protein, we probed the secondary structure of the protein-bound DHBV varepsilon  RNA (Dvarepsilon ) and observed a marked conformational change compared to free Dvarepsilon RNA. Several initiation-competent mutant RNAs with a different free-state structure were similarly altered, whereas a binding-competent but initiation-deficient variant was not, indicating the importance of the rearrangement for replication initiation and suggesting a mechanistic coupling to encapsidation.


* Corresponding author. Mailing address: Department of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany. Phone and Fax: 49-761-270 3507. E-mail: nassal2{at}ukl.uni-freiburg.de.


Molecular and Cellular Biology, November 1998, p. 6265-6272, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Nelissen, F. H. T., van Gammeren, A. J., Tessari, M., Girard, F. C., Heus, H. A., Wijmenga, S. S. (2008). Multiple segmental and selective isotope labeling of large RNA for NMR structural studies. Nucleic Acids Res 36: e89-e89 [Abstract] [Full Text]  
  • Lin, L., Wan, F., Hu, J. (2008). Functional and Structural Dynamics of Hepadnavirus Reverse Transcriptase during Protein-Primed Initiation of Reverse Transcription: Effects of Metal Ions. J. Virol. 82: 5703-5714 [Abstract] [Full Text]  
  • Stahl, M., Beck, J., Nassal, M. (2007). Chaperones Activate Hepadnavirus Reverse Transcriptase by Transiently Exposing a C-Proximal Region in the Terminal Protein Domain That Contributes to {varepsilon} RNA Binding. J. Virol. 81: 13354-13364 [Abstract] [Full Text]  
  • Petzold, K., Duchardt, E., Flodell, S., Larsson, G., Kidd-Ljunggren, K., Wijmenga, S., Schleucher, J. (2007). Conserved nucleotides in an RNA essential for hepatitis B virus replication show distinct mobility patterns. Nucleic Acids Res 35: 6854-6861 [Abstract] [Full Text]  
  • Abraham, T. M., Loeb, D. D. (2007). The Topology of Hepatitis B Virus Pregenomic RNA Promotes Its Replication. J. Virol. 81: 11577-11584 [Abstract] [Full Text]  
  • Stahl, M., Retzlaff, M., Nassal, M., Beck, J. (2007). Chaperone activation of the hepadnaviral reverse transcriptase for template RNA binding is established by the Hsp70 and stimulated by the Hsp90 system. Nucleic Acids Res 35: 6124-6136 [Abstract] [Full Text]  
  • Girard, F. C., Ottink, O. M., Ampt, K. A.M., Tessari, M., Wijmenga, S. S. (2007). Thermodynamics and NMR studies on Duck, Heron and Human HBV encapsidation signals. Nucleic Acids Res 0: gkm131v1-12 [Abstract] [Full Text]  
  • Flodell, S., Petersen, M., Girard, F., Zdunek, J., Kidd-Ljunggren, K., Schleucher, J., Wijmenga, S. (2006). Solution structure of the apical stem-loop of the human hepatitis B virus encapsidation signal. Nucleic Acids Res 34: 4449-4457 [Abstract] [Full Text]  
  • Hu, J., Boyer, M. (2006). Hepatitis B Virus Reverse Transcriptase and {varepsilon} RNA Sequences Required for Specific Interaction In Vitro. J. Virol. 80: 2141-2150 [Abstract] [Full Text]  
  • Melegari, M., Wolf, S. K., Schneider, R. J. (2005). Hepatitis B Virus DNA Replication Is Coordinated by Core Protein Serine Phosphorylation and HBx Expression. J. Virol. 79: 9810-9820 [Abstract] [Full Text]  
  • Hu, J., Flores, D., Toft, D., Wang, X., Nguyen, D. (2004). Requirement of Heat Shock Protein 90 for Human Hepatitis B Virus Reverse Transcriptase Function. J. Virol. 78: 13122-13131 [Abstract] [Full Text]  
  • Hu, K., Beck, J., Nassal, M. (2004). SELEX-derived aptamers of the duck hepatitis B virus RNA encapsidation signal distinguish critical and non-critical residues for productive initiation of reverse transcription. Nucleic Acids Res 32: 4377-4389 [Abstract] [Full Text]  
  • Beck, J., Nassal, M. (2003). Efficient Hsp90-independent in Vitro Activation by Hsc70 and Hsp40 of Duck Hepatitis B Virus Reverse Transcriptase, an Assumed Hsp90 Client Protein. J. Biol. Chem. 278: 36128-36138 [Abstract] [Full Text]  
  • Chen, S.-Y., Kao, C.-F., Chen, C.-M., Shih, C.-M., Hsu, M.-J., Chao, C.-H., Wang, S.-H., You, L.-R., Lee, Y.-H. W. (2003). Mechanisms for Inhibition of Hepatitis B Virus Gene Expression and Replication by Hepatitis C Virus Core Protein. J. Biol. Chem. 278: 591-607 [Abstract] [Full Text]  
  • Flodell, S., Schleucher, J., Cromsigt, J., Ippel, H., Kidd-Ljunggren, K., Wijmenga, S. (2002). The apical stem-loop of the hepatitis B virus encapsidation signal folds into a stable tri-loop with two underlying pyrimidine bulges. Nucleic Acids Res 30: 4803-4811 [Abstract] [Full Text]  
  • Beck, J., Vogel, M., Nassal, M. (2002). dNTP versus NTP discrimination by phenylalanine 451 in duck hepatitis B virus P protein indicates a common structure of the dNTP-binding pocket with other reverse transcriptases. Nucleic Acids Res 30: 1679-1687 [Abstract] [Full Text]  
  • Beck, J., Nassal, M. (2001). Reconstitution of a Functional Duck Hepatitis B Virus Replication Initiation Complex from Separate Reverse Transcriptase Domains Expressed in Escherichia coli. J. Virol. 75: 7410-7419 [Abstract] [Full Text]  
  • Schaaf, S. G., Beck, J., Nassal, M. (1999). A Small 2'-OH- and Base-dependent Recognition Element Downstream of the Initiation Site in the RNA Encapsidation Signal Is Essential for Hepatitis B Virus Replication Initiation. J. Biol. Chem. 274: 37787-37794 [Abstract] [Full Text]  
  • Beterams, G., Nassal, M. (2001). Significant Interference with Hepatitis B Virus Replication by a Core-nuclease Fusion Protein. J. Biol. Chem. 276: 8875-8883 [Abstract] [Full Text]