Structural basis for persulfide-sensing specificity in a transcriptional regulator
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...
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Published in | Nature chemical biology Vol. 17; no. 1; pp. 65 - 70 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Nature Publishing Group
01.01.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 D.A.C., B.J.C.W., Y.Z. and C.D. conducted biochemical and chemical studies and G.G.-G. solved the crystal structures. D.A.C. and D.P.G. conceptualized the study and supervised the research. D.P.G. was responsible for direction and resource acquisition. D.A.C. and D.P.G. wrote the manuscript, and all authors edited and reviewed it. Author contributions |
ISSN: | 1552-4450 1552-4469 |
DOI: | 10.1038/s41589-020-00671-9 |