title: Mechanism of the All-α to All-β Conformational Transition of RfaH-CTD: Molecular Dynamics Simulation and Markov State Model.
abstract: The C-terminal domain of the bacterial transcription antiterminator RfaH undergoes a dramatic all-α-helix to all-β-barrel transition when released from its N-terminal domain. These two distinct folding patterns correspond to different functions: the all-α state acts as an essential regulator of transcription to ensure RNA polymerase binding, whereas the all-β state operates as an activator of translation by interacting with the ribosomal protein S10 and recruits ribosomal mRNA. Accordingly, this drastic conformational change enables RfaH to physically couple the transcription and translation processes in gene expression. To understand the mechanism behind this extraordinary functionally relevant structural transition, we constructed Markov state models using an adaptive seeding method. The constructed models highlight several parallel folding pathways with heterogeneous molecular mechanisms, which reveal the folding kinetics and atomic details of the conformational transition.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.|Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University , 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University , 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Jingkang
authors.initials: J
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.|School of Life Science and Technology, Shanghai Tech University , Shanghai 200031, China.
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.|School of Life Science and Technology, Shanghai Tech University , Shanghai 200031, China.
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang