Structural determinants that target the hepatitis C virus core protein to lipid droplets

Boulant, S., Montserret, R., Hope, R. G., Ratinier, M., Targett-Adams, P., Lavergne, J.-P., Penin, F. and McLauchlan, J. (2006) Structural determinants that target the hepatitis C virus core protein to lipid droplets. Journal of Biological Chemistry, 281(31), pp. 22236-22247. (doi:10.1074/jbc.M601031200) (PMID:16704979)

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Abstract

Hepatitis C virus core protein is targeted to lipid droplets, which serve as intracellular storage organelles, by its C-terminal domain, termed D2. From circular dichroism and nuclear magnetic resonance analyses, we demonstrate that the major structural elements within D2 consist of two amphipathic α-helices (Helix I and Helix II) separated by a hydrophobic loop. Both helices require a hydrophobic environment for folding, indicating that lipid interactions contribute to their structural integrity. Mutational studies revealed that a combination of Helix I, the hydrophobic loop, and Helix II is essential for efficient lipid droplet association and pointed to an in-plane membrane interaction of the two helices at the phospholipid layer interface. Aside from lipid droplet association, membrane interaction of D2 is necessary for folding and stability of core following maturation at the endoplasmic reticulum membrane by signal peptide peptidase. These studies identify critical determinants within a targeting domain that enable trafficking and attachment of a viral protein to lipid droplets. They also serve as a unique model for elucidating the specificity of protein-lipid interactions between two membrane-bound organelles.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ratinier, Dr Maxime and Hope, Dr Graham and McLauchlan, Professor John
Authors: Boulant, S., Montserret, R., Hope, R. G., Ratinier, M., Targett-Adams, P., Lavergne, J.-P., Penin, F., and McLauchlan, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:The American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:16 May 2006

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn MclauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH