title: Structural elucidation of a novel mechanism for the bacteriophage-based inhibition of the RNA degradosome.
abstract: In all domains of life, the catalysed degradation of RNA facilitates rapid adaptation to changing environmental conditions, while destruction of foreign RNA is an important mechanism to prevent host infection. We have identified a virus-encoded protein termed gp37/Dip, which directly binds and inhibits the RNA degradation machinery of its bacterial host. Encoded by giant phage фKZ, this protein associates with two RNA binding sites of the RNase E component of the Pseudomonas aeruginosa RNA degradosome, occluding them from substrates and resulting in effective inhibition of RNA degradation and processing. The 2.2 Å crystal structure reveals that this novel homo-dimeric protein has no identifiable structural homologues. Our biochemical data indicate that acidic patches on the convex outer surface bind RNase E. Through the activity of Dip, фKZ has evolved a unique mechanism to down regulate a key metabolic process of its host to allow accumulation of viral RNA in infected cells.
authors.affiliation: Laboratory of Gene Technology, KU Leuven, Leuven, Belgium.|Division of Bacterial diseases, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Van den Bossche
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Hardwick
authors.affiliation: Laboratory of Gene Technology, KU Leuven, Leuven, Belgium.|Division of Bacterial diseases, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Ceyssens
authors.affiliation: Laboratory of Gene Technology, KU Leuven, Leuven, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Hendrix
authors.affiliation: Laboratory of Gene Technology, KU Leuven, Leuven, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Voet
authors.affiliation: Laboratory of Gene Technology, KU Leuven, Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Dendooven
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Bandyra
authors.affiliation: Biochemistry, Molecular and Structural Biology Scetion, KU Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: De Maeyer
authors.affiliation: Laboratory of Food Microbiology, KU Leuven, Leuven, Belgium.
authors.forename: Abram
authors.initials: A
authors.lastname: Aertsen
authors.affiliation: Biomedical Research Institute, University of Hasselt, Diepenbeek, Belgium.|Transnational University Limburg, University of Hasselt, Diepenbeek, Belgium.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Noben
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ben F
authors.initials: BF
authors.lastname: Luisi
authors.affiliation: Laboratory of Gene Technology, KU Leuven, Leuven, Belgium.
authors.forename: Rob
authors.identifier: 0000-0001-7377-1314
authors.initials: R
authors.lastname: Lavigne
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000037:antagonists & inhibitors*; D006790:Host-Parasite Interactions; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D011117:Polyribonucleotide Nucleotidyltransferase / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017105:Pseudomonas Phages / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000821:virology*; D020365:RNA Helicases / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D014764:Viral Proteins; C111244:degradosome; D011117:Polyribonucleotide Nucleotidyltransferase; D004722:Endoribonucleases; C022537:ribonuclease E; D020365:RNA Helicases
keywords: Pseudomonas aeruginosa; RNA degradosome; RNA metabolism; bacteriophage; biochemistry; infectious disease; microbiology; protein-protein interactions; virus