| Structural highlights
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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Bacterial transcription is regulated by the alarmone ppGpp, which binds near the catalytic site of RNA polymerase (RNAP) and modulates its activity. We show that the DksA protein is a crucial component of ppGpp-dependent regulation. The 2.0 A resolution structure of Escherichia coli DksA reveals a globular domain and a coiled coil with two highly conserved Asp residues at its tip that is reminiscent of the transcript cleavage factor GreA. This structural similarity suggests that DksA coiled coil protrudes into the RNAP secondary channel to coordinate a ppGpp bound Mg2+ ion with the Asp residues, thereby stabilizing the ppGpp-RNAP complex. Biochemical analysis demonstrates that DksA affects transcript elongation, albeit differently from GreA; augments ppGpp effects on initiation; and binds directly to RNAP, positioning the Asp residues near the active site. Substitution of these residues eliminates the synergy between DksA and ppGpp. Thus, the secondary channel emerges as a common regulatory entrance for transcription factors.
Regulation through the secondary channel--structural framework for ppGpp-DksA synergism during transcription.,Perederina A, Svetlov V, Vassylyeva MN, Tahirov TH, Yokoyama S, Artsimovitch I, Vassylyev DG Cell. 2004 Aug 6;118(3):297-309. PMID:15294156[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ 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
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