title: The crystal structure of the anti-σ factor CnrY in complex with the σ factor CnrH shows a new structural class of anti-σ factors targeting extracytoplasmic function σ factors.
abstract: Gene expression in bacteria is regulated at the level of transcription initiation, a process driven by σ factors. The regulation of σ factor activity proceeds from the regulation of their cytoplasmic availability, which relies on specific inhibitory proteins called anti-σ factors. With anti-σ factors regulating their availability according to diverse cues, extracytoplasmic function σ factors (σ(ECF)) form a major signal transduction system in bacteria. Here, structure:function relationships have been characterized in an emerging class of minimal-size transmembrane anti-σ factors, using CnrY from Cupriavidus metallidurans CH34 as a model. This study reports the 1.75-Å-resolution structure of CnrY cytosolic domain in complex with CnrH, its cognate σ(ECF), and identifies a small hydrophobic knob in CnrY as the major determinant of this interaction in vivo. Unsuspected structural similarity with the molecular switch regulating the general stress response in α-proteobacteria unravels a new class of anti-σ factors targeting σ(ECF). Members of this class carry out their function via a 30-residue stretch that displays helical propensity but no canonical structure on its own.
authors.affiliation: Université Grenoble Alpes, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, and Institut de Biologie Structurale, F-38000 Grenoble, France. Electronic address: antoine.maillard@ibs.fr.
authors.forename: Antoine P
authors.initials: AP
authors.lastname: Maillard
authors.affiliation: Université Grenoble Alpes, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, and Institut de Biologie Structurale, F-38000 Grenoble, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Girard
authors.affiliation: Université Grenoble Alpes, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, and Institut de Biologie Structurale, F-38000 Grenoble, France.
authors.forename: Widade
authors.initials: W
authors.lastname: Ziani
authors.affiliation: Université Grenoble Alpes, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, and Institut de Biologie Structurale, F-38000 Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit-Härtlein
authors.affiliation: Université Grenoble Alpes, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, and Institut de Biologie Structurale, F-38000 Grenoble, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Kahn
authors.affiliation: Université Grenoble Alpes, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, and Institut de Biologie Structurale, F-38000 Grenoble, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Covès
mesh_terms: D018360:Crystallography, X-Ray; D049921:Cupriavidus / Q000737:chemistry / Q000201:enzymology*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D012808:Sigma Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D012097:Repressor Proteins; D012808:Sigma Factor
keywords: bacterial transcription; metal resistance; protein:protein interaction; sigma factor; transmembrane signaling