The conserved GTPase HflX is a ribosome splitting factor that binds to the E-site of the bacterial ribosome
Loading...
Date
2016
Authors
Coatham, Mackenzie L.
Brandon, Harland E.
Fischer, Jeffrey J.
Schummer, Tobias
Wieden, Hans-Joachim
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract
Using 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.
Description
Sherpa Romeo green journal. Permission to archive final published verison
Keywords
GTPase , Guanosine triphosphatase , Ribosomes , Ribosome , E-site , Splitting factor , Antibiotics , HflX
Citation
Coatham, 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/gkv1524