The conserved GTPase HflX is a ribosome splitting factor that binds to the E-site of the bacterial ribosome

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dc.contributor.authorCoatham, Mackenzie L.
dc.contributor.authorBrandon, Harland E.
dc.contributor.authorFischer, Jeffrey J.
dc.contributor.authorSchummer, Tobias
dc.contributor.authorWieden, Hans-Joachim
dc.date.accessioned2017-03-17T22:01:06Z
dc.date.available2017-03-17T22:01:06Z
dc.date.issued2016
dc.descriptionSherpa Romeo green journal. Permission to archive final published verisonen_US
dc.description.abstractUsing a combination of biochemical, structural probing and rapid kinetics techniques we reveal for the first time that the universally conserved translational GTPase (trGTPase) HflX binds to the E-site of the 70S ribosome and that its GTPase activity is modulated by peptidyl transferase centre (PTC) and peptide exit tunnel (PET) binding antibiotics, suggesting a previously undescribed mode of action for these antibiotics. Our rapid kinetics studies reveal that HflX functions as a ribosome splitting factor that disassembles the 70S ribosomes into its subunits in a nucleotide dependent manner. Furthermore, our probing and hydrolysis studies show that the ribosome is able to activate trGTPases bound to its E-site. This is, to our knowledge, the first case in which the hydrolytic activity of a translational GTPase is not activated by the GTPase activating centre (GAC) in the ribosomal A-site. Furthermore, we provide evidence that the bound state of the PTC is able to regulate the GTPase activity of E-site bound HflX.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationCoatham, M.L., Brandon, H.E., Fischer, J.J., Schummer, T., & Wieden, H. (2016). The conserved GTPase HflX is a ribosome splitting factor that binds to the E-site of the bacterial ribosome. Nucleic Acids Research, 44(4), 1952-1963. doi:10.1093/nar/gkv1524en_US
dc.identifier.urihttps://hdl.handle.net/10133/4804
dc.language.isoen_USen_US
dc.publisherOxford University Pressen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Albertaen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.urlhttps://doi.org/10.1093/nar/gkv1524
dc.subjectGTPaseen_US
dc.subjectGuanosine triphosphataseen_US
dc.subjectRibosomesen_US
dc.subjectRibosomeen_US
dc.subjectE-siteen_US
dc.subjectSplitting factoren_US
dc.subjectAntibioticsen_US
dc.subjectHflXen_US
dc.titleThe conserved GTPase HflX is a ribosome splitting factor that binds to the E-site of the bacterial ribosomeen_US
dc.typeArticleen_US
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