Sigma factor

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Structure of sigma factor of E.Coli RNAP (grey) in complex with promoter DNA and ethylene glycol (PDB code 4lup).

Drag the structure with the mouse to rotate

1 Overview
2 Function and Structure
- 2.1 Domain Strucure & DNA interactions
- 2.2 Transcription Bubble
3 Restriction
- 3.1 Comformational and Autoinhibitory
- 3.2 anti-σ's
4 Gene Regulation and Differentiation
5 3D structures of sigma factor

Overview

Sigma (σ) factor is the peoptide subunit needed for the initiation of RNA transcription in prokaryotic organisms . As opposed to eukaryotes, who utilize a variety of proteins to initiate gene transcription, prokaryotic transcription is initiated almost completely by a σ-factor. The large and biologically essential protein, RNA polymerase (RNAP), contains one σ-subunit, which binds , located upstream of transcription start sites.

Function and Structure

The σ-factor performs two chief functions: to direct the catalytic core of RNAP to the promotoer upstream of the +1 start site of transcription, and finally to assist in the initiation of strand seperation of double-helical DNA, forming the transcription "bubble."[1] Each gene promoter utilizes a specific promoter region about 40 bp upstream of the transcription start site, and therefore different σ-factors play a role in the regulation of different genes [2]. This process, which includes association of the σ-factor with RNAP to recognize and open DNA at the promoter site, followed by dissociation of the σ to allow elongation, which can then activate additional RNAP enzymes, is referred to as the σ-cycle [3].

Domain Strucure & DNA interactions

There are many types of σ-subunits, and each recognizes a unique promoter sequence. Furthmore, each unique σ is composed of a variable number of structured domains. The simplest σ-factors have two domains, few have three, and most, called housekeeping σ-factors, have 4 domains, given the names σ(4), σ(3), σ(2), and σ(1.1) [1,3]. All domains are linked by very flexible peptide linkers which can extend very long distances. Each of these domains utilizes DNA-binding determinants, or domains that recognize specific sequences and conformations in DNA. Most commonly, these recognized sequences occur at the -35 and -10 locations upstream of the +1 site. One such DNA-binding motif, the helix-turn-helix motif (), helps specifically recognize DNA promoters at both the -35 and -10 positions [1]. This HTH motif, used by most σ-factors, maintains its specificity and accuracy by binding in the major groove of DNA, where it can interact with the base pairs in the DNA double-helix. In many prokaryotes, these portions of DNA maintain consensus adenosine and thymine sequences [1,2], such as .

Transcription Bubble

The , also referred to as the open complex is formed through the common housekeeping σ factors which unwind about 13 bp of duplex DNA in an ATP independent process. Research has shown that σ factors require invariant basic and aromatic residues (Phe, Tyr, Trp) critical for this formation [1]. The process of bubble formation begins at the -11 formation (usually A) and propogates to +1 site, through a phenomenon called , which interrupts the stacking interactions stabilizing the double helix conformation [1]. As this process occurs and the DNA transitions into the open promoter complex, certain RNAP-σ contacts are lost, initiating the dissociation of σ. In summary, the processes of -35 and -10 motif sequence recognition and helix strand separation are coupled by the σ factor.

Restriction

Initiation of prokaryotic transcription requires cooperation between the σ peptide and RNAP. Without these fundamental interactions, no transcription is possible.

Comformational and Autoinhibitory

Normally, σ-factor domains cannot bind to promoters on their own. These domains usually are placed in very compacted positions relative to each other, a conformation that buries DNA-binding determinants. This type of restriction is called conformational restriction[1]. Additionally, in housekeeping σs, a domain called the σ(1.1) stabilizes the compact conformation mentioned above, thereby preventing any promoter recognition. This method of restricting the binding abilities of isolated σ's is called autoinhibitory inhibition[1].

anti-σ's

An additional method of restriction is through the action of anti-σ's, which act by making stable interactions with σ-domains, such as σ (4), which allows them to make energy-favorable interactions with RNAP residues. This causes a cascading "peeling off" effect of other σ-domains from the RNAP, preventing any interaction with duplex DNA and inhibiting transcription in an analogous process to competitive inhibition [3].

Gene Regulation and Differentiation

Since σ-factors are exclusively linked to gene expression in prokaryotic organisms, the variety of σ-factors in a cell dictate how and what genes are transcribed. Specialized function in cells, therefore, is highly moderated by its arsenal of σ-subunits. In fact, cellular development and differentiation are directly impacted and carried out by "cascades" of σ-factors. In the early stages of development, early genes[2] are transcribed by basic bacterial σ-factors. These genes are therefore transcribed to give new σ-factors, which in turn activate additional genes, and so on [2]. This process of σ-factor cascades demonstrates the versatile and essential biologic functions of the RNAP subunit, σ.

3D structures of sigma factor

Sigma factor 3D structures

References

1. Felklistov, Andrey, Brian D. Sharon, Seth A. Darst, and Carol A. Gross. "Bacterial Sigma Factors: A Historical, Structural, and Genomic Perspective." The Annual Review of Microbiology 68 (2014): 357-76.

2. Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. 3rd ed. Hoboken, NJ: Wiley, 2008.

3. Mooney, R. A., S. A. Darst, and R. Landick. "Sigma and RNA Polymerase: An On-again, Off-again Relationship?" Molecular Cell 20.3 (2005): 335-45.

Proteopedia Page Contributors and Editors (what is this?)

Wally Novak, Michal Harel

Retrieved from "http://52.214.119.220/wiki/index.php/Sigma_factor"

Category: Topic Page

@@ Line 34: / Line 34: @@
 </StructureSection>
-==3D structures of sigma factor==
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-{{#tree:id=OrganizedByTopic|openlevels=0|
-*Sigma factor
-**[[1ku2]] – TaSF region 1.2-3.1 – ''Thermus aquaticus''<br />
-**[[1ku3]] – TaSF region 4 (mutant)<br />
-**[[3les]] – TaSF residues 93-271<br />
-**[[1sig]] – EcSF – ''Escherichia coli''<br />
-**[[2mao]] – EcSF region 2 - NMR<br />
-**[[1tty]] – TmSF-70 region 4 – ''Thermotoga maritima''<br />
-**[[2k6x]] – TmSF-70 region 1.1 (mutant) - NMR<br />
-**[[2ahq]] – AaSF-54 C terminal – ''Aquifex aeolicus'' - NMR<br />
-**[[2k9l]], [[2k9m]] – AaSF-54 core domain - NMR<br />
-**[[3mzy]] – SF-H – ''Fusobacterium nucleatum''<br />
-**[[1h3l]] – ScSF N terminal – ''Streptomyces coelicolor''<br />
-**[[5fgm]] – ScSF-R region 4<br />
-**[[5mww]] – BsSF-A region 1.1 - ''Bacillus subtilis'' - NMR <br />
-**[[5xe7]] – MtSF-J – ''Mycobacterium tuberculosis''<br />
-*Sigma factor complex with DNA
-**[[3ugo]], [[3ugp]] - TaSF region 2 + DNA<br />
-**[[4ki2]] - TaSF region 2-3 + DNA<br />
-**[[2h27]] – EcSF-E region 4 + DNA<br />
-**[[2map]] – EcSF region 2 + DNA - NMR<br />
-**[[1ku7]] – EcSF region 4 (mutant) + DNA <br />
-**[[2o8k]], [[2o9l]] – AaSF-54 C terminal + DNA - NMR<br />
-**[[5ui5]] – AaSF RpoN residues 61-398 + DNA <br />
-*Sigma factor complex with protein
-**[[3lev]] – TaSF residues 93-271 + antibody<br />
-**[[1l9u]] – TaSF region 1.1-4 + RNAP subunits α,β,β’,ω<br />
-**[[1or7]] – EcSF-E + σ-E factor negative regulatory protein <br />
-**[[4lup]] – EcSF residues 3-92 + EcSF region 2 <br />
-**[[1tlh]] – EcSF ProD region 4 + anti-σ factor<br />
-**[[2p7v]] – EcSF ProD region 4 + regulator of σ D<br />
-**[[4yg2]], [[5uag]], [[5uaj]], [[5uaq]] – EcSF ProD + RNAP subunits α,β,β’,ω  <br />
-**[[5ui8]] – EcSF-45 + RNAP subunits α,β,β’,ω  <br />
-**[[4mex]], [[4kmu]], [[4kn4]], [[4kn7]], [[5uac]], [[5uah]], [[5ual]], [[4zh3]], [[4zh4]] – EcSF ProD + RNAP subunits α,β,β’,ω + antibiotic <br />
-**[[4xsx]], [[4xsy]], [[4xsz]] – EcSF ProD + RNAP subunits α,β,β’,ω + antibiotic <br />
-**[[6byu]] – EcSF ProD + RNAP subunits α,β,β’,ω + ppApp <br />
-**[[4mey]], [[4ljz]], [[4lk1]], [[6cux]] – EcSF ProD + RNAP subunits α,β,β’,ω <br />
-**[[6c9y]], [[6ca0]] – EcSF ProD + RNAP subunits α,β,β’,ω - Cryo EM<br />
-**[[5byh]] – EcSF-45 + RNAP subunits α,β,β’,ω <br />
-**[[5nwt]] – EcSF-54 + RNAP subunits α,β,β’,ω <br />
-**[[5w1s]] – EcSF RpoD + RNAP subunits α,β,β’ + TraR<br />
-**[[5vsw]] – EcSF RpoD + RNAP subunits α,β,β’ + DnaK suppressor protein<br />
-**[[5w1t]] – EcSF RpoD + RNAP subunits α,β,β’ + RpoZ + DnaK suppressor protein<br />
-**[[4lk0]], [[4llg]], [[4yfk]], [[4yfn]], [[4yfx]], [[4zh2]] – EcSF ProD + EcRNAP subunits α,β,β’,ω + RNAP inhibitor<br />
-**[[1rp3]], [[1sc5]] – AaSF-28 + anti-σ factor FLGM <br />
-**[[5wuq]] – BsSF SIGW + anti-σ factor RSIW  <br />
-**[[3hug]] – MtSF-L + membrane protein <br />
-**[[4nqw]] – MtSF-K region 4 + anti-σ factor<br />
-**[[4x8k]] – MtSF-A region 2 + RBPA<br />
-**[[6fbv]] – MtSF-A + RNAP subunits α,β,β’,ω - SP Cryo EM<br />
-**[[6c05]], [[6c06]] – MtSF-A + RNAP subunits α,β,β’,ω + RbpA - Cryo EM<br />
-**[[3wod]], [[2a6e]], [[2cw0]], [[5tmf]] – TtSF + RNAP subunits α,β,β’,ω - ''Thermus thermophilus'' <br />
-**[[4mq9]], [[2a68]], [[2a69]], [[2a6h]], [[3dxj]], [[3eql]] – TtSF ProD + RNAP subunits α,β,β’,ω + antibiotic <br />
-**[[2be5]] – TtSF + RNAP subunits α,β,β’,ω + inhibitor<br />
-**[[5tmc]] – TtSF-A + RNAP subunits α,β,β’,ω + protein + G4P<br />
-**[[5xj0]] – TtSF-A + RNAP subunits α,β,β’,ω + GP39 + GP76<br />
-**[[5x22]] – TtSF-A + RNAP subunits α,β,β’,ω + GpA + CMPcPP<br />
-**[[4lk0]], [[4llg]], [[4yfk]], [[4yfn]], [[4yfx]], [[4zh2]] – EcSF ProD + EcRNAP subunits α,β,β’,ω + RNAP inhibitor<br />
-**[[4cxf]] – SF CNRH + CNRY – ''Cupriavidus metallidurans''<br />
-**[[4g6d]], [[4g8x]], [[4g94]] – SF ProD region 4 + Orf067 – ''Staphylococcus aureus''<br />
-**[[5yix]] – SF RpoD + GCRA - ''Caulobacter crescentus''<br />
-*Sigma factor complex with protein and DNA
-**[[4oio]], [[4g7h]], [[4g7o]], [[4g7z]], [[4q4z]], [[4q5s]] – TtSF SIGA + RNAP subunits α,β,β’,ω + DNA<br />
-**[[1smy]] – TtSF + RNAP subunits α,β,β’,ω + G4P<br />
-**[[3n97]] – TaSF region 4 + RNAP subunits α + DNA<br />
-**[[4xlp]], [[4xlq]], [[5tjg]] – TaSF SIGA + RNAP subunits α,β,β’,ω + DNA   <br />
-**[[1l9z]] – TaSF + RNAP subunits α,β,β’,ω + DNA – Cryo EM  <br />
-**[[4xlr]], [[4xls]] – TaSF-A + RNAP subunits α,β,β’,ω + CarD-like transcriptional regulator + DNA   <br />
-**[[1rio]] - TaSF region 4 + repression protein CI + DNA<br />
-**[[3iyd]] – EcSF ProD + EcRNAP subunits α,β,β’,ω + catabolite gene activator + DNA<br />
-**[[4jk1]], [[4jk2]], [[4jkr]] – EcSF ProD + EcRNAP subunits α,β,β’,ω + G4P<br />
-**[[4yln]], [[4ylo]], [[4ylp]] – EcSF ProD + EcRNAP subunits α,β,β’,ω + DNA<br />
-**[[5nss]] – EcSF-54 + EcRNAP subunits α,β,β’,ω + phage shock protein F + DNA - Cryo EM<br />
-**[[5nsr]], [[6gh6]], [[6gh5]], [[6gfw]] – EcSF-54 + EcRNAP subunits α,β,β’,ω + DNA - Cryo EM<br />
-**[[5voi]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA <br />
-**[[5d4c]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + CTP + ATP<br />
-**[[5d4d]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + CTP + NAD<br />
-**[[5d4e]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + CTP + dephosphate-CoA<br />
-**[[5uha]] – MtSF-A + MtRNAP subunits α,β,β’,ω + DNA <br />
-**[[6c04]] – MtSF-A + RNAP subunits α,β,β’,ω + RbpA + DNA - Cryo EM<br />
-**[[5uhe]], [[5uhf]] – MtSF SIGA + MtRNAP subunits α,β,β’,ω + DNA + inhibitor<br />
-**[[5tw1]], [[6cce]] – MsSF-A + MtRNAP subunits α,β,β’,ω + DNA + peptide - ''Mycobacterium smegmatis''<br />
-**[[5vi8]] – MsSF-A + MsRNAP subunits α,β,β’,ω + DNA <br />
-**[[6ccv]] – MsSF-A + MtRNAP subunits α,β,β’,ω + DNA + peptide + RbpA <br />
-*Sigma factor complex with protein and DNA and antibiotics
-**[[4oin]], [[4oip]], [[4oiq]], [[4oir]] – TtSF-A + RNAP subunits α,β,β’,ω + antibiotic + DNA<br />
-**[[6cuu]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + antibiotic<br />
-**[[5uhg]] – MtSF-A + MtRNAP subunits α,β,β’,ω + DNA + antibiotic + inhibitor<br />
-**[[5uhb]] – MtSF-A + MtRNAP subunits α,β,β’,ω + DNA + antibiotic<br />
-**[[6bzo]] – MtSF-A + RNAP subunits α,β,β’,ω + RbpA + DNA + antibiotic - Cryo EM<br />
-**[[6ccf]] – MsSF-A + MtRNAP subunits α,β,β’,ω + DNA + peptide + antibiotic<br />
-*Sigma factor complex with protein, DNA and RNA
-**[[5vi5]] – MsSF-A + MsRNAP subunits α,β,β’,ω + RbpA + DNA + RNA<br />
-**[[4xln]] – TaSF-A + RNAP subunits α,β,β’,ω + DNA + RNA  <br />
-**[[5ipl]], [[5ipm]], [[5ipn]] – EcSF RpoS + EcRNAP subunits α,β,β’,ω + DNA + RNA<br />
-**[[6b6h]] – EcSF RpoD + EcRNAP subunits α,β,β’,ω + DNA + RNA - Cryo EM<br />
-**[[5e17]], [[5e18]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + RNA<br />
-**[[5x22]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + RNA + CMPPP<br />
-**[[5vo8]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + RNA + GTP<br />
-**[[5x21]] – TtSF-A + TtRNAP subunits α,β,β’,ω + DNA + RNA + antibiotic<br />
-**[[5i2d]] – TtSF-A + TtRNAP subunits α,β,β’,ω + transcriptional regulator + DNA + RNA<br />
-**[[5uh5]], [[5uh8]], [[5uh9]] – MtSF-A + MtRNAP subunits α,β,β’,ω + DNA + RNA<br />
-**[[5uh6]], [[5uhc]], [[5uhd]], [[5x21]] – MtSF-A + TtRNAP subunits α,β,β’,ω + DNA + RNA + antibiotic<br />
-}}
 == References ==