Structural basis for persulfide-sensing specificity in a transcriptional regulator.
Acinetobacter baumannii
/ genetics
Amino Acid Sequence
Bacterial Proteins
/ chemistry
Binding Sites
Cloning, Molecular
Crystallography, X-Ray
Cysteine
/ chemistry
Disulfides
/ chemistry
Escherichia coli
/ genetics
Gene Expression
Gene Expression Regulation, Bacterial
Genetic Vectors
/ chemistry
Glutathione
/ chemistry
Kinetics
Models, Molecular
Oxidation-Reduction
Promoter Regions, Genetic
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Quinone Reductases
/ chemistry
Recombinant Proteins
/ chemistry
Sequence Alignment
Sequence Homology, Amino Acid
Sulfides
/ chemistry
Sulfur
/ chemistry
Thermodynamics
Transcription, Genetic
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
23
03
2020
accepted:
11
09
2020
pubmed:
28
10
2020
medline:
20
2
2021
entrez:
27
10
2020
Statut:
ppublish
Résumé
Cysteine thiol-based transcriptional regulators orchestrate the coordinated regulation of redox homeostasis and other cellular processes by 'sensing' or detecting a specific redox-active molecule, which in turn activates the transcription of a specific detoxification pathway. The extent to which these sensors are truly specific in cells for a singular class of reactive small-molecule stressors, for example, reactive oxygen or sulfur species, is largely unknown. Here, we report structural and mechanistic insights into the thiol-based transcriptional repressor SqrR, which reacts exclusively with oxidized sulfur species such as persulfides, to yield a tetrasulfide bridge that inhibits DNA operator-promoter binding. Evaluation of crystallographic structures of SqrR in various derivatized states, coupled with the results of a mass spectrometry-based kinetic profiling strategy, suggest that persulfide selectivity is determined by structural frustration of the disulfide form. These findings led to the identification of an uncharacterized repressor from the bacterial pathogen Acinetobacter baumannii as a persulfide sensor.
Identifiants
pubmed: 33106663
doi: 10.1038/s41589-020-00671-9
pii: 10.1038/s41589-020-00671-9
pmc: PMC7746634
mid: NIHMS1643689
doi:
Substances chimiques
Bacterial Proteins
0
Disulfides
0
Recombinant Proteins
0
Sulfides
0
persulfides
0
Sulfur
70FD1KFU70
Quinone Reductases
EC 1.6.99.-
sulfide quinone reductase
EC 1.8.5.-
Glutathione
GAN16C9B8O
Cysteine
K848JZ4886
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
65-70Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM109825
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118157
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM131994
Pays : United States
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