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Chapter 3 : Regulation by Alternative Sigma Factors
Category: Microbial Genetics and Molecular Biology
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This chapter summarizes the alternative sigma factors of the two model organisms (Escherichia coli and Bacillus subtilis), describes the types of regulatory pathways that have evolved to control σ activity, and presents a glimpse at some recently discovered variations on these already established themes. In addition, many stress-induced proteins were initially identified using proteomics and were named for the inducing stress(es). Examples include general stress proteins (GSP) and heat shock proteins (HSP). Regulation of σS proteolysis plays a major role in controlling activation of this stress response by starvation for diverse nutrients and several other stresses. Although the full implications of the complex regulatory architecture are not yet clear, a number of advantages are apparent. First, the branched pathway allows for integration of two distinct classes of signals and, within each signaling pathway, there are likely multiple regulatory targets thereby enabling a further diversity of inputs. Second, the use of reversible protein modifications (phosphorylation/ dephosphorylation) enables a rapid response to changing conditions and also enables the system to be rapidly shut off once homeostatic conditions are restored. Third, the use of reversible protein modifications to regulate activity may ultimately be more energy efficient than those systems that rely instead on destruction of an anti-σ with the consequent need for new protein synthesis to reset the system. Sporulation in B. subtilis was the first process unambiguously shown to rely on alternative s factors for its execution and thus holds a special place in the historical development of σ factor biology.
Overview of bacterial σ factor structure-function relationships. (A) The interaction of a generic σ70 family protein with a promoter sequence is illustrated. Structural studies reveal three conserved domains in bacterial σ factors (σ2, σ3, and σ4) corresponding roughly to regions of sequence conservation. Conserved motifs in region 4.2 (within a classical helix-turn-helix unit) recognize the –35 element while –10 region recognition and melting is mediated by residues from regions 2.3 and 2.4. Region 3 contributes to the recognition of sequences adjacent to the –10 element in “extended –10” promoters. Bacterial σ factors are divided into distinct structural groups based on the presence or absence of conserved sequence regions 1 though 4. Note that ECF σ factors have only regions 2 and 4 and, in the case of the bipartite σ YvrI/YvrHa, these two functions are in separate polypeptides. (B) A schematic illustrating the relative position of the three conserved σ70 domains with the holoenzyme complex. Major roles of each region are illustrated including protein regions implicated in core-binding, –35 and –10 element recognition and promoter melting, and contacts with regulatory proteins (anti-σ factors) and DNA-binding transcription activators.
Modes of regulation for σ factors. A generic hypothetical σ factor (σQ) is shown together with a schematic illustration of the various modes of regulating σ factor activity. Activity can be regulated at the following levels: transcription (e.g., by positive feedback regulation), translation, protein processing (conversion of pro-σ to functional protein; not illustrated), protein activity (by anti-σ RsiQ), or by controlled proteolysis of either the σ or anti-σ. As illustrated here, expression of the sigQ-rsiQ operon by σQ generates both positive feedback loops (autoregulation of σQ) and a negative feedback loop (RsiQ). This type of regulation is common amongst ECF σ factors. In other cases, other members of the σ regulon may act as either positive or negative feedback regulators.
Mechanisms for controlling the activity of anti-σ factors. Anti-σ factors can be regulated by: (i) proteolytic destruction (e.g., RIP of RseA to release σE); (ii) protein-protein interactions such as transmembrane signaling as illustrated for the ferric-citrate mediated induction of the σFecI regulon mediated by FecA and FecR; (iii) secretion from the cell as in the example of FlgM which is exported through the completed hook-basal body (HBB); or (iv) sequestration by an anti-anti-σ (e.g., partnerswitching mechanism as illustrated for B. subtilis σB). See text for details.
σ70 family factors of E. coli and B. subtilis