Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 2, Pages 501-516Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkz1133
Keywords
-
Categories
Funding
- National Science Foundation CAREER Award [CLP 1846908]
- National Institute of Health through the Nebraska Center for Integrated Biomolecular Communication [P20 GM113126]
- National Institute of Health through the Nebraska Redox Biology Center [P30 GM103335]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC0276SF00515]
Ask authors/readers for more resources
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 angstrom-resolution crystal structure of the [4Fe-4S] cluster-bound (holo-) WhiB1 in complex with the C-terminal domain of the sigma(70)-family primary sigma factor sigma(A) of M. tuberculosis containing the conserved region 4 (sigma(A)(4)). Region 4 of the sigma(70)-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 sigma(A)(4). The complex structure, however, unexpectedly reveals that the interaction between WhiB1 and sigma(A)(4) is dominated by hydrophobic residues in the [4Fe-4S] cluster binding pocket, distinct from previously characterized canonical sigma(70)(4)-bound transcription activators. Furthermore, we show that holo-WhiB1 represses transcription by interaction with sigma(A)(4)in vitro and that WhiB1 must interact with sigma(A)(4) 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 sigma(A)(4)-dependent transcription activators.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available