title: Structure and signaling mechanism of a zinc-sensory diguanylate cyclase.
abstract: Diguanylate cyclases synthesize the second messenger c-di-GMP, which in turn governs a plethora of physiological processes in bacteria. Although most diguanylate cyclases harbor sensory domains, their input signals are largely unknown. Here, we demonstrate that diguanylate cyclase DgcZ (YdeH) from Escherichia coli is regulated allosterically by zinc. Crystal structures show that the zinc ion is bound to the 3His/1Cys motif of the regulatory chemoreceptor zinc-binding domain, which mediates subunit contact within the dimeric enzyme. In vitro, zinc reversibly inhibits DgcZ with a subfemtomolar Ki constant. In vivo, bacterial biofilm formation is modulated by externally applied zinc in a DgcZ- and c-di-GMP-dependent fashion. The study outlines the structural principles of this zinc sensor. Zinc binding seems to regulate the activity of the catalytic GGDEF domains by impeding their mobility and thus preventing productive encounter of the two GTP substrates.
authors.affiliation: Focal Area of Structural Biology and Biophysics, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Zähringer
authors.forename: Egidio
authors.initials: E
authors.lastname: Lacanna
authors.forename: Urs
authors.initials: U
authors.lastname: Jenal
authors.forename: Tilman
authors.initials: T
authors.lastname: Schirmer
authors.forename: Alex
authors.initials: A
authors.lastname: Boehm
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000595:Amino Acid Sequence; D018441:Biofilms; D020134:Catalytic Domain; D002614:Chelating Agents / Q000737:chemistry; D018360:Crystallography, X-Ray; D004492:Edetic Acid / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019761:Phosphorus-Oxygen Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D015398:Signal Transduction; D015032:Zinc / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D029968:Escherichia coli Proteins; D004492:Edetic Acid; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D015032:Zinc