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

Hao Wu, Qiang Liu, Delia Casas-Pastor, Franziska Dürr, Thorsten Mascher, Georg Fritz

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 σ2 and σ4 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 σ4 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.

Original languageEnglish
Pages (from-to)498-514
Number of pages17
JournalMolecular Microbiology
Volume112
Issue number2
DOIs
Publication statusPublished - Aug 2019
Externally publishedYes

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Terminal Repeat Sequences
Structural Models
Alanine
Amino Acids
Protein Domains

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Wu, Hao ; Liu, Qiang ; Casas-Pastor, Delia ; Dürr, Franziska ; Mascher, Thorsten ; Fritz, Georg. / The role of C-terminal extensions in controlling ECF σ factor activity in the widely conserved groups ECF41 and ECF42. In: Molecular Microbiology. 2019 ; Vol. 112, No. 2. pp. 498-514.
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The role of C-terminal extensions in controlling ECF σ factor activity in the widely conserved groups ECF41 and ECF42. / Wu, Hao; Liu, Qiang; Casas-Pastor, Delia; Dürr, Franziska; Mascher, Thorsten; Fritz, Georg.

In: Molecular Microbiology, Vol. 112, No. 2, 08.2019, p. 498-514.

Research output: Contribution to journalArticle

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