title: Long-range allosteric signaling in red light-regulated diguanylyl cyclases.
abstract: Nature has evolved an astonishingly modular architecture of covalently linked protein domains with diverse functionalities to enable complex cellular networks that are critical for cell survival. The coupling of sensory modules with enzymatic effectors allows direct allosteric regulation of cellular signaling molecules in response to diverse stimuli. We present molecular details of red light-sensing bacteriophytochromes linked to cyclic dimeric guanosine monophosphate-producing diguanylyl cyclases. Elucidation of the first crystal structure of a full-length phytochrome with its enzymatic effector, in combination with the characterization of light-induced changes in conformational dynamics, reveals how allosteric light regulation is fine-tuned by the architecture and composition of the coiled-coil sensor-effector linker and also the central helical spine. We anticipate that consideration of molecular principles of sensor-effector coupling, going beyond the length of the characteristic linker, and the appreciation of dynamically driven allostery will open up new directions for the design of novel red light-regulated optogenetic tools.
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Petersgasse 12/II, 8010 Graz, Austria.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Gourinchas
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Petersgasse 12/II, 8010 Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Etzl
authors.affiliation: Center for Integrated Protein Science Munich, Technische Universität München, Department of Chemistry, Lichtenbergstraße 4, 85748 Garching, Germany.; Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Göbl
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Petersgasse 12/II, 8010 Graz, Austria.
authors.forename: Uršula
authors.initials: U
authors.lastname: Vide
authors.affiliation: Center for Integrated Protein Science Munich, Technische Universität München, Department of Chemistry, Lichtenbergstraße 4, 85748 Garching, Germany.; Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.; Institute of Molecular Biology and Biochemistry, Medical University of Graz, Harrachgasse 21/III, 8010 Graz, Austria.
authors.forename: Tobias
authors.identifier: 0000-0002-9725-5231
authors.initials: T
authors.lastname: Madl
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Petersgasse 12/II, 8010 Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Winkler
mesh_terms: D000494:Allosteric Regulation; D034241:Alteromonadaceae / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006162:Guanylate Cyclase / Q000737:chemistry*; D008027:Light; D000072417:Protein Domains; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D006162:Guanylate Cyclase
keywords: HDX-MS; SAXS; allostery; c-di-GMP; diguanylate cyclase; dynamics; effector; phytochrome; sensor