title: The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control.
abstract: C-di-GMP-which is produced by diguanylate cyclases (DGC) and degraded by specific phosphodiesterases (PDEs)-is a ubiquitous second messenger in bacterial biofilm formation. In Escherichia coli, several DGCs (YegE, YdaM) and PDEs (YhjH, YciR) and the MerR-like transcription factor MlrA regulate the transcription of csgD, which encodes a biofilm regulator essential for producing amyloid curli fibres of the biofilm matrix. Here, we demonstrate that this system operates as a signalling cascade, in which c-di-GMP controlled by the DGC/PDE pair YegE/YhjH (module I) regulates the activity of the YdaM/YciR pair (module II). Via multiple direct interactions, the two module II proteins form a signalling complex with MlrA. YciR acts as a connector between modules I and II and functions as a trigger enzyme: its direct inhibition of the DGC YdaM is relieved when it binds and degrades c-di-GMP generated by module I. As a consequence, YdaM then generates c-di-GMP and-by direct and specific interaction-activates MlrA to stimulate csgD transcription. Trigger enzymes may represent a general principle in local c-di-GMP signalling.
authors.affiliation: Institut für Biologie-Mikrobiologie, Freie Universität Berlin, Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lindenberg
authors.forename: Gisela
authors.initials: G
authors.lastname: Klauck
authors.forename: Christina
authors.initials: C
authors.lastname: Pesavento
authors.forename: Eberhard
authors.initials: E
authors.lastname: Klauck
authors.forename: Regine
authors.initials: R
authors.lastname: Hengge
mesh_terms: D018441:Biofilms / Q000254:growth & development; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D048168:Escherichia coli K12 / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D015290:Second Messenger Systems; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C499694:CsgD protein, E coli; D029968:Escherichia coli Proteins; C430113:Gmr protein, E coli; C451279:MlrA protein, E coli; D046912:Multiprotein Complexes; D015534:Trans-Activators; C062025:bis(3',5')-cyclic diguanylic acid; D019761:Phosphorus-Oxygen Lyases; C517137:YdaM protein, E coli; D006152:Cyclic GMP