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Journal of Virology, September 2005, p. 11353-11365, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11353-11365.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Hepatitis C Virus Core Protein Is a Dimeric Alpha-Helical Protein Exhibiting Membrane Protein Features

Steeve Boulant,1 Christophe Vanbelle,1,{dagger} Christine Ebel,2 François Penin,1 and Jean-Pierre Lavergne1*

Institut de Biologie et Chimie des Protéines, UMR5086 CNRS-Université Claude Bernard Lyon I, IFR 128 Biosciences Lyon-Gerland, 7 Passage du Vercors, 69367 Lyon Cedex 07, France,1 Institut de Biologie Structurale, UMR5075 CEA-CNRS-UJF, 41 Rue Jules Horowitz, 38027 Grenoble Cedex 1, France2

Received 18 February 2005/ Accepted 7 April 2005

The building block of hepatitis C virus (HCV) nucleocapsid, the core protein, together with viral RNA, is composed of different domains involved in RNA binding and homo-oligomerization. The HCV core protein 1-169 (CHCV169) and its N-terminal region from positions 1 to 117 (CHCV117) were expressed in Escherichia coli and purified to homogeneity suitable for biochemical and biophysical characterizations. The overall conformation and the oligomeric properties of the resulting proteins CHCV169 and CHCV117 were investigated by using analytical centrifugation, circular dichroism, intrinsic fluorescence measurements, and limited proteolysis. Altogether, our results show that core protein (CHCV169) behaves as a membranous protein and forms heterogeneous soluble micelle-like aggregates of high molecular weight in the absence of detergent. In contrast, it behaves, in the presence of mild detergent, as a soluble, well-folded, noncovalent dimer. Similar to findings observed for core proteins of HCV-related flaviviruses, the HCV core protein is essentially composed of {alpha}-helices (50%). In contrast, CHCV117 is soluble and monodispersed in the absence of detergent but is unfolded. It appears that the folding of the highly basic domain from positions 2 to 117 (2-117 domain) depends on the presence of the 117-169 hydrophobic domain, which contains the structural determinants ensuring the binding of core with cellular membranes. Finally, our findings provide valuable information for further investigations on isolated core protein, as well as for attempts to reconstitute nucleocapsid particles in vitro.

* Corresponding author. Mailing address: Institut de Biologie et Chimie des Protéines, UMR5086 CNRS-Université Claude Bernard Lyon I, IFR 128 Biosciences Lyon-Gerland, 7 Passage du Vercors, 69367 Lyon Cedex 07, France. Phone: 33-472-722-645. Fax: 33-472-722-604. E-mail: jp.lavergne{at}ibcp.fr.

{dagger} Present address: ANIMET/IFR 62, INSERM, UCBL, Faculté de Médecine RTH Laennec, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France.

Journal of Virology, September 2005, p. 11353-11365, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11353-11365.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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