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Publication Abstract from PubMed

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

Structural basis for transcription activation by Crl through tethering of sigma(S) and RNA polymerase.,Cartagena AJ, Banta AB, Sathyan N, Ross W, Gourse RL, Campbell EA, Darst SA Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):18923-18927. doi:, 10.1073/pnas.1910827116. Epub 2019 Sep 4. PMID:31484766^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.