| Structural highlights
5w1t is a 14 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 5vsw, 5w1s |
| Gene: | rpoA, pez, phs, sez, b3295, JW3257 (ECOLI), rpoB, groN, nitB, rif, ron, stl, stv, tabD, b3987, JW3950 (ECOLI), rpoC, tabB, b3988, JW3951 (ECOLI), rpoD, alt, b3067, JW3039 (ECOLI), dksA, b0145, JW0141 (ECOLI) |
| Activity: | DNA-directed RNA polymerase, with EC number 2.7.7.6 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[DKSA_ECOLI] Transcription factor that acts by binding directly to the RNA polymerase (RNAP). Required for negative regulation of rRNA expression and positive regulation of several amino acid biosynthesis promoters. Also required for regulation of fis expression. Binding to RNAP disrupts interaction of RNAP with DNA, inhibits formation of initiation complexes, and amplifies effects of ppGpp and the initiating NTP on rRNA transcription. Inhibits transcript elongation, exonucleolytic RNA cleavage and pyrophosphorolysis, and increases intrinsic termination. Also involved, with RecN, in repair of DNA double-strand breaks.[1] [2] [3] [4] [5] [RPOZ_ECOLI] Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.[HAMAP-Rule:MF_00366] [RPOA_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. This subunit plays an important role in subunit assembly since its dimerization is the first step in the sequential assembly of subunits to form the holoenzyme.[HAMAP-Rule:MF_00059] [RPOC_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322] [RPOB_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] [RPOD_ECOLI] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This is the primary sigma factor of this bacterium.
Publication Abstract from PubMed
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.
Allosteric Effector ppGpp Potentiates the Inhibition of Transcript Initiation by DksA.,Molodtsov V, Sineva E, Zhang L, Huang X, Cashel M, Ades SE, Murakami KS Mol Cell. 2018 Mar 1;69(5):828-839.e5. doi: 10.1016/j.molcel.2018.01.035. Epub, 2018 Feb 22. PMID:29478808[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Paul BJ, Barker MM, Ross W, Schneider DA, Webb C, Foster JW, Gourse RL. DksA: a critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. Cell. 2004 Aug 6;118(3):311-22. PMID:15294157 doi:http://dx.doi.org/10.1016/j.cell.2004.07.009
- ↑ Meddows TR, Savory AP, Grove JI, Moore T, Lloyd RG. RecN protein and transcription factor DksA combine to promote faithful recombinational repair of DNA double-strand breaks. Mol Microbiol. 2005 Jul;57(1):97-110. PMID:15948952 doi:http://dx.doi.org/10.1111/j.1365-2958.2005.04677.x
- ↑ Mallik P, Paul BJ, Rutherford ST, Gourse RL, Osuna R. DksA is required for growth phase-dependent regulation, growth rate-dependent control, and stringent control of fis expression in Escherichia coli. J Bacteriol. 2006 Aug;188(16):5775-82. PMID:16885445 doi:http://dx.doi.org/10.1128/JB.00276-06
- ↑ Furman R, Sevostyanova A, Artsimovitch I. Transcription initiation factor DksA has diverse effects on RNA chain elongation. Nucleic Acids Res. 2012 Apr;40(8):3392-402. doi: 10.1093/nar/gkr1273. Epub 2011, Dec 30. PMID:22210857 doi:http://dx.doi.org/10.1093/nar/gkr1273
- ↑ Perederina A, Svetlov V, Vassylyeva MN, Tahirov TH, Yokoyama S, Artsimovitch I, Vassylyev DG. Regulation through the secondary channel--structural framework for ppGpp-DksA synergism during transcription. Cell. 2004 Aug 6;118(3):297-309. PMID:15294156 doi:10.1016/j.cell.2004.06.030
- ↑ Molodtsov V, Sineva E, Zhang L, Huang X, Cashel M, Ades SE, Murakami KS. Allosteric Effector ppGpp Potentiates the Inhibition of Transcript Initiation by DksA. Mol Cell. 2018 Mar 1;69(5):828-839.e5. doi: 10.1016/j.molcel.2018.01.035. Epub, 2018 Feb 22. PMID:29478808 doi:http://dx.doi.org/10.1016/j.molcel.2018.01.035
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