title: Role of the PFXFATG[G/Y] Motif in the Activation of SdrG, a Response Regulator Involved in the Alphaproteobacterial General Stress Response.
abstract: Two-component systems are major signal transduction pathways, which consist of histidine kinases and response regulators that communicate through phosphorylation. Here, we highlight a distinct class of single-domain response regulators containing the PFXFATG[G/Y] motif that are activated by a mechanism distinct from the Y-T coupling described for prototypical receiver domains. We first solved the structures of inactive and active SdrG, a representative of the FAT GUY family, and then biochemically and genetically characterized variants in which residues in this motif were mutated. Our results support a model of activation mainly driven by a conserved lysine and reveal that the rotation of the threonine induces the reorganization of several aromatic residues in and around the PFXFATG[G/Y] motif to generate intermediates resembling those occurring during classical Y-T coupling. Overall, this helps define a new subfamily of response regulators that emerge as important players in physiological adaptation.
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland; Institute of Molecular Biology and Biophysics, ETH Zurich, Hönggerbergring 64, 8093 Zürich, Switzerland. Electronic address: sebastien.campagne@mol.biol.ethz.ch.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Campagne
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dintner
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gottschlich
authors.affiliation: Institute of Molecular Biology and Biophysics, ETH Zurich, Hönggerbergring 64, 8093 Zürich, Switzerland.
authors.forename: Maxence
authors.initials: M
authors.lastname: Thibault
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bortfeld-Miller
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaczmarczyk
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Francez-Charlot
authors.affiliation: Institute of Molecular Biology and Biophysics, ETH Zurich, Hönggerbergring 64, 8093 Zürich, Switzerland.
authors.forename: Frédéric H-T
authors.initials: FH
authors.lastname: Allain
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Vorholt
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020578:Sphingomonas / Q000737:chemistry* / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D013816:Thermodynamics; D013912:Threonine / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D013912:Threonine; D008239:Lysine