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Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):18923-18927. doi: 10.1073/pnas.1910827116. Epub 2019 Sep 4.

Structural basis for transcription activation by Crl through tethering of σS and RNA polymerase.

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Tri-Institutional Training Program in Chemical Biology, The Rockefeller University, New York, NY 10065.
Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065.
Department of Bacteriology, University of Wisconsin, Madison, WI 53706.
Pharmaceutical Sciences Division, University of Wisconsin, Madison, WI 53706.
Great Lakes Bioenergy Research Center, University of Wisconsin, Madison, WI 53706.
Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;


In bacteria, a primary σ-factor associates with the core RNA polymerase (RNAP) to control most transcription initiation, while alternative σ-factors are used to coordinate expression of additional regulons in response to environmental conditions. Many alternative σ-factors are negatively regulated by anti-σ-factors. In Escherichia coli, Salmonella enterica, and many other γ-proteobacteria, the transcription factor Crl positively regulates the alternative σS-regulon by promoting the association of σS with RNAP without interacting with promoter DNA. The molecular mechanism for Crl activity is unknown. Here, we determined a single-particle cryo-electron microscopy structure of Crl-σS-RNAP in an open promoter complex with a σS-regulon promoter. In addition to previously predicted interactions between Crl and domain 2 of σSS 2), the structure, along with p-benzoylphenylalanine cross-linking, reveals that Crl interacts with a structural element of the RNAP β'-subunit that we call the β'-clamp-toe (β'CT). Deletion of the β'CT decreases activation by Crl without affecting basal transcription, highlighting the functional importance of the Crl-β'CT interaction. We conclude that Crl activates σS-dependent transcription in part through stabilizing σS-RNAP by tethering σS 2 and the β'CT. We propose that Crl, and other transcription activators that may use similar mechanisms, be designated σ-activators.


Crl; RNA polymerase; RpoS; bacterial stress response; cryo-electron microscopy


Conflict of interest statement

The authors declare no conflict of interest.

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