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J Virol, June 1998, p. 4997-5005, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mapping of Homologous Interaction Sites in the Hepatitis B Virus Core Protein

Sabine König,1 Gertrud Beterams,2 and Michael Nassal1,2,*

Zentrum für Molekulare Biologie, University of Heidelberg, D-69120 Heidelberg,1 and Department of Internal Medicine II, University Hospital, University of Freiburg, D-79106 Freiburg,2 Germany

Received 15 December 1997/Accepted 17 February 1998

Hepatitis B virus consists of an outer envelope and an inner capsid, or core, that wraps around the small genome plus the viral replication enzyme. The icosahedrally symmetric nucleocapsid is assembled from multiple dimeric subunits of a single 183-residue capsid protein, which must therefore contain interfaces for monomer dimerization and for dimer multimerization. The atomic structure of the protein is not known, but electron microscopy-based image reconstructions suggested a hammerhead shape for the dimer and, very recently, led to a tentative model for the main chain trace. Here we used a combination of interaction screening techniques and functional analyses of core protein variants to define, at the primary sequence level, the regions that mediate capsid assembly. Both the two-hybrid system and the pepscan technique identified a strongly interacting region I between amino acids (aa) 78 and 117 that probably forms part of the dimer interface. Surprisingly, mutations in this region, in the context of a C-terminally truncated but assembly-competent core protein variant, had no detectable effect on assembly. By contrast, mutations in a second region, bordered by aa 113 and 143, markedly influenced capsid stability, strongly suggesting that this region II is the main contributor to dimer multimerization. Based on the electron microscopic data, it must therefore be located at the basal tips of the dimer, experimentally supporting the proposed main chain trace.

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

J Virol, June 1998, p. 4997-5005, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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