An α-helix to β-barrel domain switch transforms the transcription factor RfaH into a translationfactor

By Björn M. Burmann, S. Knauer, A. Sevostyanova, K. Schweimer, R. Mooney, R. Landick, I. Artsimovitch, P. Rösch. 2012

222 citations recorded by the source corpus.

SUMMARY NusG homologs regulate transcription and coupled processes in all living organisms. The Escherichia coli (E. coli) two-domain paralogs NusG and RfaH have conformationally identical N-terminal domains (NTDs) but dramatically different carboxy-terminal domains (CTDs), a β-barrel in NusG and an α-hairpin in RfaH. Both NTDs interact with elongating RNA polymerase (RNAP) to reduce pausing. In NusG, NTD and CTD are completely independent, and NusG-CTD interacts with termination factor Rho or ribosomal protein S10. In contrast, RfaH-CTD makes extensive contacts with RfaH-NTD to mask an RNAP-binding site therein. Upon RfaH interaction with its DNA target, the operon polarity suppressor (ops) DNA, RfaH-CTD is released, allowing RfaH-NTD to bind to RNAP. Here we show that the released RfaH-CTD completely refolds from an all-α to an all-β conformation identical to that of NusG-CTD. As a consequence, RfaH-CTD binding to S10 is enabled and translation of RfaH-controlled operons is strongly potentiated.

Subfields: Genetics, Molecular Biology

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Citations in the corpus

Predicting multiple conformations via sequence clustering and AlphaFold2 (2023, neutral): “In the active state, the CTD unbinds and forms a β-sheet that is homologous to the transcription factor NusG (CTD PDB: 2LCL) 22 . b , AF-Cluster returns structure models that include both the autoinhibited and the active state with high confidence.”
The universally-conserved transcription factor RfaH is recruited to a hairpin structure of the non-template DNA strand (2018, methodology): “To evaluate the roles of individual ops bases in vivo we used a luciferase (lux) reporter system (Burmann et al., 2012) in which RfaH increases expression ~40-fold with the wild-type (WT) ops (Figure 2B).”
Coevolution‐derived native and non‐native contacts determine the emergence of a novel fold in a universally conserved family of transcription factors (2022, background): “In fact, recent experimental work has demonstrated that the ends of the αCTD hairpin are largely unstructured in solution.(7,18) Furthermore, it has been shown that an exactly solvable model of helicalcoil-sheet transitions displays cooperativity in its temperature-induced folding from helical to ex”
Extant fold-switching proteins are widespread (2018, background): “One obvious example is RfaH, which functions as both a transcription factor and a translation factor (10).”