Structure of the full-length HCV IRES in solution

• DOI: 10.1038/ncomms2611
• Publication Date: 2013-03-19T10:58:07Z
• Authors: Julien Pérard; Cédric Leyrat; Florence Baudin; Emmanuel Drouet; Marc Jamin
• Keywords: Small Angle; 0301 basic medicine; 570; Molecular Biology/Structural Biology [q-bio.BM]; MESH: X-Ray Diffraction; Hepacivirus; Molecular Dynamics Simulation; 540; [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry; 3. Good health; [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]; 03 medical and health sciences; MESH: Scattering; X-Ray Diffraction; Scattering, Small Angle; MESH: 5' Untranslated Regions; MESH: Hepacivirus; MESH: Molecular Dynamics Simulation; 5' Untranslated Regions; MESH: Ribosomes; Ribosomes; MESH: Scattering, Small Angle

The 5'-untranslated region of the hepatitis C virus genome contains an internal ribosome entry site (IRES) that initiates cap-independent translation of the viral RNA. Until now, the structural characterization of the entire (IRES) remained limited to cryo-electron microscopy reconstructions of the (IRES) bound to different cellular partners. Here we report an atomic model of free full-length hepatitis C virus (IRES) refined by selection against small-angle X-ray scattering data that incorporates the known structures of different fragments. We found that an ensemble of conformers reproduces small-angle X-ray scattering data better than a single structure suggesting in combination with molecular dynamics simulations that the hepatitis C virus (IRES) is an articulated molecule made of rigid parts that move relative to each other. Principal component analysis on an ensemble of physically accessible conformers of hepatitis C virus (IRES) revealed dominant collective motions in the molecule, which may underlie the conformational changes occurring in the (IRES) molecule upon formation of the initiation complex.