A two-state model for helicase translocation and unwinding of nucleic acids

TL;DR

This paper introduces a two-state model for helicase translocation and unwinding of nucleic acids, extending previous models to include state switching, and compares predictions with experimental data on NS3 helicase, highlighting both agreements and limitations.

Contribution

The paper develops a two-state helicase model that captures unwinding speed and fluctuations, extending prior models and relating to the flashing ratchet mechanism.

Findings

Model predicts unwinding speed and fluctuations.

Comparison with NS3 helicase data supports key model features.

Experimental variability limits definitive conclusions.

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 of 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-J\"ulicher 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.