Public Time:
2021-04-27 00:00:00
Journal:
PNAS
doi: 10.1073/pnas.2024324118
Author:
Ilona Christy Unarta,Siqin Cao,Shintaroh Kubo,Wei Wang,Peter Pak-Hang Cheung,Xin Gao,Shoji Takada,Xuhui Huang
Summary:
The initiation of bacterial transcription requires DNA loading via flexible loading gate of the RNA polymerase complex, consisting of the clamp and β-lobe domain. While the clamp is important in transcription initiation, the role of β-lobe remains unclear. Using quasi-Markov State Models (qMSMs) constructed from molecular dynamics simulations, we showed that the opening of β-lobe is orders of magnitude faster than that of the clamp, which depends on the structure of Switch 2. Strikingly, opening of the β-lobe is sufficient geometrically to accommodate DNA loading even when the clamp is partially closed. These two observations highlight β-lobe’s critical role allowing DNA loading during initiation. Thus, β-lobe is a promising target for antibiotics. qMSM also provides a promising tool investigating biomolecular dynamics.
MD simulation trajectories have been deposited in Open Science Framework (DOI: [10.17605/OSF.IO/HK9F7][1]) ([89][2]).
[1]: https://doi.org/10.17605/OSF.IO/HK9F7
[2]: #ref-89