Computationally exploring the mechanism of bacteriophage T7 gp4 helicase translocating along ssDNA
Date
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Bacteriophage T7 gp4 helicase has served as a model system for understanding mechanisms of hexameric replicative helicase translocation. The mechanistic basis of how nucleoside 5′-triphosphate hydrolysis and translocation of gp4 helicase are coupled is not fully resolved. Here, we used a thermodynamically benchmarked coarse-grained protein force field, Associative memory, Water mediated, Structure and Energy Model (AWSEM), with the single-stranded DNA (ssDNA) force field 3SPN.2C to investigate gp4 translocation. We found that the adenosine 5′-triphosphate (ATP) at the subunit interface stabilizes the subunit–subunit interaction and inhibits subunit translocation. Hydrolysis of ATP to adenosine 5′-diphosphate enables the translocation of one subunit, and new ATP binding at the new subunit interface finalizes the subunit translocation. The LoopD2 and the N-terminal primase domain provide transient protein–protein and protein–DNA interactions that facilitate the large-scale subunit movement. The simulations of gp4 helicase both validate our coarse-grained protein–ssDNA force field and elucidate the molecular basis of replicative helicase translocation.
Description
Advisor
Degree
Type
Keywords
Citation
Jin, Shikai, Bueno, Carlos, Lu, Wei, et al.. "Computationally exploring the mechanism of bacteriophage T7 gp4 helicase translocating along ssDNA." Proceedings of the National Academy of Sciences, 119, no. 32 (2022) National Academy of Sciences: https://doi.org/10.1073/pnas.2202239119.