6ONU

Complex structure of WhiB1 and region 4 of SigA in P21 space group.

Summary for 6ONU

• Entry DOI: 10.2210/pdb6onu/pdb
• Related: 6ONO
• Descriptor: Transcriptional regulator WhiB1, RNA polymerase sigma factor SigA, IRON/SULFUR CLUSTER, ... (5 entities in total)
• Functional Keywords: iron-sulfur cluster, transcription regulation, redox-sensing, transcription
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 8
• Total formula weight: 90473.40

Authors

Wan, T.,Li, S.R.,Beltran, D.G.,Schacht, A.,Becker, D.C.,Zhang, L.M. (deposition date: 2019-04-22, release date: 2019-11-27, Last modification date: 2024-10-23)

Primary citation

Wan, T.,Li, S.,Beltran, D.G.,Schacht, A.,Zhang, L.,Becker, D.F.,Zhang, L.
Structural basis of non-canonical transcriptional regulation by the sigma A-bound iron-sulfur protein WhiB1 in M. tuberculosis.
Nucleic Acids Res., 48:501-516, 2020

PubMed Abstract: WhiB1 is a monomeric iron-sulfur cluster-containing transcription factor in the WhiB-like family that is widely distributed in actinobacteria including the notoriously persistent pathogen Mycobacterium tuberculosis (M. tuberculosis). WhiB1 plays multiple roles in regulating cell growth and responding to nitric oxide stress in M. tuberculosis, but its underlying mechanism is unclear. Here we report a 1.85 Å-resolution crystal structure of the [4Fe-4S] cluster-bound (holo-) WhiB1 in complex with the C-terminal domain of the σ70-family primary sigma factor σA of M. tuberculosis containing the conserved region 4 (σA4). Region 4 of the σ70-family primary sigma factors is commonly used by transcription factors for gene activation, and holo-WhiB1 has been proposed to activate gene expression via binding to σA4. The complex structure, however, unexpectedly reveals that the interaction between WhiB1 and σA4 is dominated by hydrophobic residues in the [4Fe-4S] cluster binding pocket, distinct from previously characterized canonical σ704-bound transcription activators. Furthermore, we show that holo-WhiB1 represses transcription by interaction with σA4in vitro and that WhiB1 must interact with σA4 to perform its essential role in supporting cell growth in vivo. Together, these results demonstrate that holo-WhiB1 regulates gene expression by a non-canonical mechanism relative to well-characterized σA4-dependent transcription activators.

PubMed: 31807774
DOI: 10.1093/nar/gkz1133

Experimental method

X-RAY DIFFRACTION (1.85 Å)