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Mol Cell. 2018 Mar 1;69(5):828-839.e5. doi: 10.1016/j.molcel.2018.01.035. Epub 2018 Feb 22.

Allosteric Effector ppGpp Potentiates the Inhibition of Transcript Initiation by DksA.

Author information

1
Department of Biochemistry and Molecular Biology, The Center for RNA Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
2
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
3
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
4
Intramural Research Program, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
5
Department of Biochemistry and Molecular Biology, The Center for RNA Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: ades@psu.edu.
6
Department of Biochemistry and Molecular Biology, The Center for RNA Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: kum14@psu.edu.

Abstract

DksA and ppGpp are the central players in the stringent response and mediate a complete reprogramming of the transcriptome. A major component of the response is a reduction in ribosome synthesis, which is accomplished by the synergistic action of DksA and ppGpp bound to RNA polymerase (RNAP) inhibiting transcription of rRNAs. Here, we report the X-ray crystal structures of Escherichia coli RNAP in complex with DksA alone and with ppGpp. The structures show that DksA accesses the template strand at the active site and the downstream DNA binding site of RNAP simultaneously and reveal that binding of the allosteric effector ppGpp reshapes the RNAP-DksA complex. The structural data support a model for transcriptional inhibition in which ppGpp potentiates the destabilization of open complexes by DksA. This work establishes a structural basis for understanding the pleiotropic effects of DksA and ppGpp on transcriptional regulation in proteobacteria.

PMID:
29478808
PMCID:
PMC5837818
DOI:
10.1016/j.molcel.2018.01.035
[Indexed for MEDLINE]
Free PMC Article

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