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Reversible fold-switching controls the functional cycle of the antitermination factor RfaH

Title data

Zuber, Philipp Konrad ; Schweimer, Kristian ; Rösch, Paul ; Artsimovitch, Irina ; Knauer, Stefan H.:
Reversible fold-switching controls the functional cycle of the antitermination factor RfaH.
Lehrstuhl Biopolymere, Universität Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany; Forschungszentrum für Bio-Makromoleküle, Universität Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany; Department of Microbiology, The Ohio State University, Columbus, OH, 43210, USA; The Center for RNA Biology, The Ohio State University, Columbus, OH, 43210, USA
In: Nature Communications. Vol. 10 (February 2019) . - No. 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.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biopolymers
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Biopolymers - Univ.-Prof. Dr. Paul Rösch
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biopolymers > Lehrstuhl Biopolymere - Apl. Prof. Dr. Birgitta Wöhrl
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 22 Feb 2019 09:12
Last Modified: 07 Jun 2019 07:28
URI: https://eref.uni-bayreuth.de/id/eprint/47506