Structure of the full-length HCV IRES in solution

Area of Science:

• Molecular Biology
• Virology
• Structural Biology

Background:

• The 5'-untranslated region of Hepatitis C virus (HCV) harbors an internal ribosome entry site (IRES).
• IRES facilitates cap-independent translation initiation of viral RNA.
• Previous structural studies of HCV IRES were limited to cryo-EM of complexes.

Purpose of the Study:

• To determine the atomic model of the free, full-length Hepatitis C virus (HCV) IRES.
• To investigate the dynamic and conformational properties of the HCV IRES.

Main Methods:

• Atomic model refinement using small-angle X-ray scattering (SAXS) data.
• Integration of known fragment structures.
• Molecular dynamics (MD) simulations.
• Principal component analysis (PCA) on conformer ensembles.

Main Results:

• An ensemble of conformers, not a single structure, best fits SAXS data.
• HCV IRES is an articulated molecule with rigid domains exhibiting relative motion.
• MD and PCA identified dominant collective motions within the IRES.

Conclusions:

• HCV IRES possesses intrinsic flexibility and dynamic conformational states.
• These motions likely play a role in forming the translation initiation complex.
• The study provides a dynamic view of IRES structure and function.