T7 RNA polymerase translocation is facilitated by a helix opening on the   fingers domain that may also prevent backtracking

doi:10.1093/nar/gkx495

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	T7 RNA polymerase translocation is facilitated by a helix opening on the fingers domain that may also prevent backtracking
	Da, Lin-Tai ; E, Chao ; Shuai, Yao ; Wu, Shaogui ; Su, Xiao-Dong ; Yu, Jin
刊名	NUCLEIC ACIDS RESEARCH
	2017
关键词	MARKOV STATE MODELS MOLECULAR-DYNAMICS STRUCTURAL BASIS CONFORMATIONAL DYNAMICS ELONGATION COMPLEXES GENOME INSTABILITY TRANSCRIPTION TRANSITION SIMULATIONS INITIATION
DOI	10.1093/nar/gkx495
英文摘要	Here, we studied the complete process of a viral T7 RNA polymerase (RNAP) translocation on DNA during transcription elongation by implementing extensive all-atom molecular dynamics (MD) simulations to construct a Markov state model (MSM). Our studies show that translocation proceeds in a Brownian motion, and the RNAP thermally transits among multiple metastable states. We observed non-synchronized backbone movements of the nucleic acid (NA) chains with the RNA translocation accomplished first, while the template DNA lagged. Notably, both the O-helix and Y-helix on the fingers domain play key roles in facilitating NA translocation through the helix opening. The helix opening allows a key residue Tyr639 to become inserted into the active site, which pushes the RNA-DNA hybrid forward. Another key residue, Phe644, coordinates the downstream template DNA motions by stacking and un-stacking with a transition nucleotide (TN) and its adjacent nucleotide. Moreover, the O-helix opening at pre-translocation (pre-trans) likely resists backtracking. To test this hypothesis, we computationally designed mutants of T7 RNAP by replacing the amino acids on the O-helix with counterpart residues from a mitochondrial RNAP that is capable of backtracking. The current experimental results support the hypothesis.; National Natural Science Foundation of China [11275022, 31270803, U1430237]; SCI(E); ARTICLE; 13; 7909-7921; 45
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/472001]
专题	生命科学学院
推荐引用方式 GB/T 7714	Da, Lin-Tai,E, Chao,Shuai, Yao,et al. T7 RNA polymerase translocation is facilitated by a helix opening on the fingers domain that may also prevent backtracking[J]. NUCLEIC ACIDS RESEARCH,2017.
APA	Da, Lin-Tai,E, Chao,Shuai, Yao,Wu, Shaogui,Su, Xiao-Dong,&Yu, Jin.(2017).T7 RNA polymerase translocation is facilitated by a helix opening on the fingers domain that may also prevent backtracking.NUCLEIC ACIDS RESEARCH.
MLA	Da, Lin-Tai,et al."T7 RNA polymerase translocation is facilitated by a helix opening on the fingers domain that may also prevent backtracking".NUCLEIC ACIDS RESEARCH (2017).