title: TRANSCRIPTION. Structures of the RNA polymerase-σ54 reveal new and conserved regulatory strategies.
abstract: Transcription by RNA polymerase (RNAP) in bacteria requires specific promoter recognition by σ factors. The major variant σ factor (σ(54)) initially forms a transcriptionally silent complex requiring specialized adenosine triphosphate-dependent activators for initiation. Our crystal structure of the 450-kilodalton RNAP-σ(54) holoenzyme at 3.8 angstroms reveals molecular details of σ(54) and its interactions with RNAP. The structure explains how σ(54) targets different regions in RNAP to exert its inhibitory function. Although σ(54) and the major σ factor, σ(70), have similar functional domains and contact similar regions of RNAP, unanticipated differences are observed in their domain arrangement and interactions with RNAP, explaining their distinct properties. Furthermore, we observe evolutionarily conserved regulatory hotspots in RNAPs that can be targeted by a diverse range of mechanisms to fine tune transcription.
authors: Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, China.
authors: Yun
authors: Y
authors: Yang
authors: Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. Department of Medicine, Imperial College London, South Kensington SW7 2AZ, UK.
authors: Vidya C
authors: VC
authors: Darbari
authors: Department of Life Sciences, Imperial College London, South Kensington SW7 2AZ, UK.
authors: Nan
authors: N
authors: Zhang
authors: Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK.
authors: Duo
authors: D
authors: Lu
authors: Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. Department of Medicine, Imperial College London, South Kensington SW7 2AZ, UK.
authors: Robert
authors: R
authors: Glyde
authors: State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, China.
authors: Yi-Ping
authors: YP
authors: Wang
authors: Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA.
authors: Jared T
authors: JT
authors: Winkelman
authors: Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA.
authors: Richard L
authors: RL
authors: Gourse
authors: Department of Biochemistry and Molecular Biology, Center for RNA Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
authors: Katsuhiko S
authors: KS
authors: Murakami
authors: Department of Life Sciences, Imperial College London, South Kensington SW7 2AZ, UK.
authors: Martin
authors: M
authors: Buck
authors: Centre for Structural Biology, Imperial College London, South Kensington SW7 2AZ, UK. Department of Medicine, Imperial College London, South Kensington SW7 2AZ, UK. xiaodong.zhang@imperial.ac.uk.
authors: Xiaodong
authors: X
authors: Zhang
mesh_terms: D018360:Crystallography, X-Ray; D004795:Enzyme Stability; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D020035:Holoenzymes / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051877:RNA Polymerase Sigma 54 / Q000737:chemistry* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D020035:Holoenzymes; D051877:RNA Polymerase Sigma 54