at Google ScholarTitle data
Zuber, Philipp ; Schweimer, Kristian ; Rösch, Paul ; Artsimovitch, Irina ; Knauer, Stefan H.:
Reversible fold-switching controls the functional cycle of the antitermination factor RfaH.
In: Nature Communications.
Vol. 10
(2019)
.
- 702.
ISSN 2041-1723
DOI: https://doi.org/10.1038/s41467-019-08567-6
Abstract in another language
RfaH, member of the NusG/Spt5 family, activates virulence genes in Gram-negative pathogens. RfaH exists in two states, with its C-terminal domain (CTD) folded either as α-helical hairpin or β-barrel. In free RfaH, the α-helical CTD interacts with, and masks the RNA polymerase binding site on, the N-terminal domain, autoinhibiting RfaH and restricting its recruitment to opsDNA sequences. Upon activation, the domains separate and the CTD refolds into the β-barrel, which recruits a ribosome, activating translation. Using NMR spectroscopy, we show that only a complete ops-paused transcription elongation complex activates RfaH, probably via a transient encounter complex, allowing the refolded CTD to bind ribosomal protein S10. We also demonstrate that upon release from the elongation complex, the CTD transforms back into the autoinhibitory α-state, resetting the cycle. Transformation-coupled autoinhibition allows RfaH to achieve high specificity and potent activation of gene expression.