Two-state model for helicase translocation and unwinding of nucleic acids

Phys Rev E Stat Nonlin Soft Matter Phys. 2008 Jun;77(6 Pt 1):061910. doi: 10.1103/PhysRevE.77.061910. Epub 2008 Jun 13.

Abstract

Helicases are molecular motors that unwind double-stranded nucleic acids (dsNA), such as DNA and RNA. Typically a helicase translocates along one of the NA single strands while unwinding and uses adenosine triphosphate (ATP) hydrolysis as an energy source. Here we model a helicase motor that can switch between two states, which could represent two different points in the ATP hydrolysis cycle. Our model is an extension of the earlier Betterton-Jülicher model of helicases to incorporate switching between two states. The main predictions of the model are the speed of unwinding of the dsNA and fluctuations around the average unwinding velocity. Motivated by a recent claim that the NS3 helicase of Hepatitis C virus follows a flashing-ratchet mechanism, we have compared the experimental results for the NS3 helicase with a special limit of our model which corresponds to the flashing-ratchet scenario. Our model accounts for one key feature of the experimental data on NS3 helicase. However, contradictory observations in experiments carried out under different conditions limit the ability to compare the model to experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Biophysics / methods
  • DNA Helicases / chemistry*
  • DNA Helicases / physiology
  • DNA, Viral / chemistry
  • Diffusion
  • Hepacivirus / enzymology
  • Hydrolysis
  • Models, Biological
  • Models, Statistical
  • Models, Theoretical
  • Nucleic Acid Conformation*
  • Nucleic Acids / chemistry*
  • Thermodynamics
  • Viral Nonstructural Proteins / metabolism

Substances

  • DNA, Viral
  • NS3 protein, hepatitis C virus
  • Nucleic Acids
  • Viral Nonstructural Proteins
  • Adenosine Triphosphate
  • DNA Helicases