Sigma factor

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Revision as of 10:21, 5 February 2020

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

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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

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

Updated on 05-February-2020

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 65: / Line 65: @@
 **[[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 />
@@ Line 82: / Line 96: @@
 **[[5xj0]] – TtSF-A + RNAP subunits α,β,β’,ω + GP39 + GP76<br />
 **[[5x22]] – TtSF-A + RNAP subunits α,β,β’,ω + GpA + CMPcPP<br />
-**[[1l9u]] – TaSF region 1.1-4 + RNAP subunits α,β,β’,ω<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 />
 **[[4cxf]] – SF CNRH + CNRY – ''Cupriavidus metallidurans''<br />
@@ Line 102: / Line 103: @@
 *Sigma factor complex with protein and DNA
-**[[1rio]] - TaSF region 4 + repression protein CI + DNA<br />
 **[[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 />
-**[[1l9u]], [[1l9z]] – TaSF + RNAP subunits α,β,β’,ω + DNA – Cryo EM  <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 />