title: Mechanistic insight into the conserved allosteric regulation of periplasmic proteolysis by the signaling molecule cyclic-di-GMP.
abstract: Stable surface adhesion of cells is one of the early pivotal steps in bacterial biofilm formation, a prevalent adaptation strategy in response to changing environments. In Pseudomonas fluorescens, this process is regulated by the Lap system and the second messenger cyclic-di-GMP. High cytoplasmic levels of cyclic-di-GMP activate the transmembrane receptor LapD that in turn recruits the periplasmic protease LapG, preventing it from cleaving a cell surface-bound adhesin, thereby promoting cell adhesion. In this study, we elucidate the molecular basis of LapG regulation by LapD and reveal a remarkably sensitive switching mechanism that is controlled by LapD's HAMP domain. LapD appears to act as a coincidence detector, whereby a weak interaction of LapG with LapD transmits a transient outside-in signal that is reinforced only when cyclic-di-GMP levels increase. Given the conservation of key elements of this receptor system in many bacterial species, the results are broadly relevant for cyclic-di-GMP- and HAMP domain-regulated transmembrane signaling.
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States.
authors.forename: Debashree
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Cooley
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States.
authors.forename: Chelsea D
authors.initials: CD
authors.lastname: Boyd
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis, United States.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Mehl
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States georgeo@dartmouth.edu.
authors.forename: George A
authors.initials: GA
authors.lastname: O'Toole
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States hs293@cornell.edu.
authors.forename: Holger
authors.initials: H
authors.lastname: Sondermann
mesh_terms: D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D008958:Models, Molecular; D009154:Mutation; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019897:Periplasm / Q000378:metabolism; D033903:Periplasmic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D011551:Pseudomonas fluorescens / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D033903:Periplasmic Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D010447:Peptide Hydrolases; D006152:Cyclic GMP
keywords: bacterial pathogens; biofilm formation; c-di-GMP; cell adhesion; signaling; transmembrane protein