The ECF Classification: A Phylogenetic Reflection of the Regulatory Diversity in the Extracytoplasmic Function σ Factor Protein Family

In order to survive, bacteria must adapt to multiple fluctuations in their environment, including coping with changes in metal concentrations. Many metals are essential for viability, since they act as cofactors of indispensable enzymes. But on the other hand, they are potentially toxic because they generate reactive oxygen species or displace other metals from proteins, turning them inactive. This dual effect of metals forces cells to maintain homeostasis using a variety of systems to import and export them. These systems are usually inducible, and their expression is regulated by metal sensors and signal-transduction mechanisms, one of which is mediated by extracytoplasmic function (ECF) sigma factors. In this review, we have focused on the metalresponsive ECF sigma factors, several of which are activated by iron depletion (FecI, FpvI and PvdS), while others are activated by excess of metals such as nickel and cobalt (CnrH), copper (CarQ and CorE) or cadmium and zinc (CorE2). We focus particularly on their physiological roles, mechanisms of action and signal transduction pathways.

Section: Regulation Of Metal Ion Homeostasis By Ecf Sigma Factorsmentioning

confidence: 99%

“…However, not all ECF sigma factors function in the same manner. A phylogenetic classification of the ECF sigma factors into 94 different groups has shed some light on the diversity of mechanisms regulating their activity and the stimuli detected (Staroń et al , ; Mascher, ; Pinto and Mascher, ).…”

Section: Regulation Of Metal Ion Homeostasis By Ecf Sigma Factorsmentioning

confidence: 99%

Metal‐responsive RNA polymerase extracytoplasmic function (ECF) sigma factors

Moraleda‐Muñoz

Marcos‐Torres

Pérez

et al. 2019

“…Analysis of nearly 3000 ECF σ sequences identified 43 distinct groups (designated ECF01 through ECF43) that encompassed 2/3 of the available sequences, with the remaining forming many smaller clusters (Staron et al , ). This classification scheme has since grown to ~ 100 distinct groups of ECF σ factors, as defined based on their protein sequences, genomic context and target promoter sequences (Pinto and Mascher, ).…”

Section: Introductionmentioning

confidence: 99%

Where to begin? Sigma factors and the selectivity of transcription initiation in bacteria

Helmann

2019

Transcription is the fundamental process that enables the expression of genetic information. DNA-directed RNA polymerase (RNAP) uses one strand of the DNA duplex as template to produce complementary RNA molecules that serve in translation (rRNA, tRNA), protein synthesis (mRNA) and regulation (sRNA). Although the RNAP core is catalytically competent for RNA synthesis, the selectivity of transcription initiation requires a sigma (σ) factor for promoter recognition and opening. Expression of alternative σ factors provides a powerful mechanism to control the expression of discrete sets of genes (a σ regulon) in response to specific nutritional, developmental or stress-related signals. Here, I review the key insights that led to the original discovery of σ factor 50 years ago and the subsequent discovery of alternative σ factors as a ubiquitous mechanism of bacterial gene regulation. These studies form a prelude to the more recent, genomics-enabled insights into the vast diversity of σ factors in bacteria.'Begin at the beginning,' the King said, very gravely, 'and go on till you come to the end: then stop.' Lewis Carroll, Alice in Wonderland

“…ECFs are regulated in response to a diverse array of cellular processes, including stress responses, iron uptake, differentiation, secondary metabolism, virulence and biofilm formation (Helmann, ; Braun et al , ; Ho and Ellermeier, ; Mascher, ; Llamas et al , ; Souza et al , ). This physiological variability is reflected by their phylogenetic diversity, as evidenced by comparative genomics analyses that classified the ECF protein family into more than 90 phylogenetically distinct groups (Staroń et al , ; Jogler et al , ; Huang et al , ; Pinto and Mascher, ).…”

Section: Introductionmentioning

confidence: 99%

The role of C‐terminal extensions in controlling ECF σ factor activity in the widely conserved groups ECF41 and ECF42

Liu

Casas-Pastor

et al. 2019

Self Cite

The activity of extracytoplasmic function σ-factors (ECFs) is typically regulated by anti-σ factors. In a number of highly abundant ECF groups, including ECF41 and ECF42, σ-factors contain fused C-terminal protein domains, which provide the necessary regulatory function instead. Here, we identified the contact interface between the C-terminal extension and the core σ-factor regions required for controlling ECF activity. We applied direct coupling analysis (DCA) to infer evolutionary covariation between contacting amino acid residues for groups ECF41 and ECF42. Mapping the predicted interactions to a recently solved ECF41 structure demonstrated that DCA faithfully identified an important contact interface between the SnoaL-like extension and the linker between the σ 2 and σ 4 domains. Systematic alanine substitutions of contacting residues support this model and suggest that this interface stabilizes a compact conformation of ECF41 with low transcriptional activity. For group ECF42, DCA supports a structural homology model for their C-terminal tetratricopeptide repeat (TPR) domains and predicts an intimate contact between the first TPR-helix and the σ 4 domain. Mutational analyses demonstrate the essentiality of the predicted interactions for ECF42 activity. These results indicate that C-terminal extensions indeed bind and regulate the core ECF regions, illustrating the potential of DCA for discovering regulatory motifs in the ECF subfamily.