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CysB is a member of the large bacterial LysR-type transcriptional regulator (LTTR) protein family. Like the majority of LTTRs, CysB functions as a homotetramer in which each subunit has an N-terminal winged-helix-turn-helix (wHTH) DNA-binding domain connected to an effector-binding domain by a helical hinge region. CysB is best known for its role in regulating the expression of genes associated with sulfur uptake and biosynthesis of cysteine in Gram-negative species such as Escherichia coli and Salmonella enterica. Activation of CysB target genes generally requires the effector N-acetyl-L-serine, which derives from an intermediate in the cysteine biosynthetic pathway. Here, we outline the established roles of CysB in controlling the cysteine regulon, complemented with an interpretation of DNA binding modes inspired by the recently published structure of full-length CysB that is consistent with the ‘sliding dimer’ model proposed for many LTTRs. Notably, CysB orthologs have been described for which N-acetyl-L-serine does not appear to be required as an effector, and CysB regulons frequently include genes that are not directly related to sulfur assimilation and cysteine biosynthesis. Examples include hslJ, which encodes a predicted membrane protein involved in novobiocin resistance in E. coli, and pqsR, encoding a transcriptional regulator involved in Pseudomonas Quinolone Signal production and virulence in Pseudomonas aeruginosa. These data suggest that CysB orthologs have diverged to ensure optimal function and incorporation in distinct gene regulatory networks.
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Versatility and Complexity: Common and Uncommon Facets of LysR-Type Transcriptional Regulators
LysR-type transcriptional regulators (LTTRs) form one of the largest families of bacterial regulators. They are widely distributed and contribute to all aspects of metabolism and physiology. Most are homotetramers, with each subunit composed of an N-terminal DNA-binding domain followed by a long helix connecting to an effector-binding domain. LTTRs typically bind DNA in the presence or absence of a small-molecule ligand (effector). In response to cellular signals, conformational changes alter DNA interactions, contact with RNA polymerase, and sometimes contact with other proteins. Many are dual-function repressor–activators, although different modes of regulation may occur at multiple promoters. This review presents an update on the molecular basis of regulation, the complexity of regulatory schemes, and applications in biotechnology and medicine. The abundance of LTTRs reflects their versatility and importance. While a single regulatory model cannot describe all family members, a comparison of similarities and differences provides a framework for future study. Expected final online publication date for the Annual Review of Microbiology, Volume 77 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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- Award ID(s):
- 2225858
- PAR ID:
- 10437916
- Date Published:
- Journal Name:
- Annual Review of Microbiology
- Volume:
- 77
- Issue:
- 1
- ISSN:
- 0066-4227
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1146/annurev-micro-050323-040543
