Structural elucidation of a novel mechanism for the bacteriophage-based inhibition of the RNA degradosome
An Van den Bossche,
Steven W Hardwick,
Pieter-Jan Ceyssens,
Hanne Hendrix,
Marleen Voet,
Tom Dendooven,
Katarzyna J Bandyra,
Marc De Maeyer,
Abram Aertsen,
Jean-Paul Noben,
Ben F Luisi,
Rob Lavigne
Affiliations
An Van den Bossche
Laboratory of Gene Technology, KU Leuven, Leuven, Belgium; Division of Bacterial diseases, Scientific Institute of Public Health, Brussels, Belgium
Steven W Hardwick
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Pieter-Jan Ceyssens
Laboratory of Gene Technology, KU Leuven, Leuven, Belgium; Division of Bacterial diseases, Scientific Institute of Public Health, Brussels, Belgium
Hanne Hendrix
Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
Marleen Voet
Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
Tom Dendooven
Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
Katarzyna J Bandyra
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Marc De Maeyer
Biochemistry, Molecular and Structural Biology Scetion, KU Leuven, Leuven, Belgium
Abram Aertsen
Laboratory of Food Microbiology, KU Leuven, Leuven, Belgium
Jean-Paul Noben
Biomedical Research Institute, University of Hasselt, Diepenbeek, Belgium; Transnational University Limburg, University of Hasselt, Diepenbeek, Belgium
Ben F Luisi
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
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.
