Structural basis of non-canonical transcriptional regulation by the σA-bound iron-sulfur protein WhiB1 in M. tuberculosis

Tao Wan, Shanren Li, Daisy Guiza Beltran, Andrew Schacht, Lu Zhang, Donald F Becker, and LiMei Zhang

Nucleic Acids Res (2020) 48(2): 501-516. doi:10.1093/nar/gkz1133

This study reports the structure of the WhiB1 bacterial transcription factor bound to the C-terminal domain of the primary sigma factor σA (σA CTD) from M. tuberculosis. This protein, like others in the Wbl protein family, contains a [4Fe-4S] cluster and is widely distributed in actinobacteria. WhiB proteins play versatile roles in diverse biological processes. WhiB1 is of particular interest because it is essential for cell growth, and it is suggested to have a role in the initiation of dormancy in response to nitric oxide (NO). NO is a potent antimicrobial chemical produced by the host to combat tuberculosis infection. Consequently, the transcription factors in the defense system of M. tuberculosis that swiftly sense and respond to NO are critical for the survival and pathogenesis of the bacterium. The reactivity of the [4Fe-4S] cluster in WhiB1 is highly selective for NO over O2, making it a specific NO sensor in aerobic bacteria.

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