Journal article
Sequestration of a dual function DNA-binding protein by Vibrio cholerae CRP
Proceedings of the National Academy of Sciences - PNAS, Vol.119(46), e2210115119
11/15/2022
DOI: 10.1073/pnas.2210115119
PMCID: PMC9674212
PMID: 36343262
Abstract
Although the mechanism by which the cyclic AMP receptor protein (CRP) regulates global gene transcription has been intensively studied for decades, new discoveries remain to be made. Here, we report that, during rapid growth, CRP associates with both the well-conserved, dual-function DNA-binding protein peptidase A (PepA) and the cell membrane. These interactions are not present under nutrient-limited growth conditions, due to post-translational modification of three lysines on a single face of CRP. Although coincident DNA binding is rare, dissociation from CRP results in increased PepA occupancy at many chromosomal binding sites and differential regulation of hundreds of genes, including several encoding cyclic dinucleotide phosphodiesterases. We show that PepA represses biofilm formation and activates motility/chemotaxis. We propose a model in which membrane-bound CRP interferes with PepA DNA binding. Under nutrient limitation, PepA is released. Together, CRP and free PepA activate a transcriptional response that impels the bacterium to seek a more hospitable environment. This work uncovers a function for CRP in the sequestration of a regulatory protein. More broadly, it describes a paradigm of bacterial transcriptome modulation through metabolically regulated association of transcription factors with the cell membrane.
Details
- Title: Subtitle
- Sequestration of a dual function DNA-binding protein by Vibrio cholerae CRP
- Creators
- Jacob A. Gibson - Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USAMichael J. Gebhardt - Boston Children's HospitalRenato E. R. S. Santos - Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USASimon L. Dove - Boston Children's HospitalPaula I. Watnick - Boston Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.119(46), e2210115119
- DOI
- 10.1073/pnas.2210115119
- PMID
- 36343262
- PMCID
- PMC9674212
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- Natl Acad Sciences
- Number of pages
- 11
- Grant note
- R01AI112652 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32 AI132120 / Harvard Bacteriology PhD Training Program
- Language
- English
- Date published
- 11/15/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984438859702771
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