Sequestration of a dual function DNA-binding protein by Vibrio cholerae CRP.
Proc Natl Acad Sci U S A
; 119(46): e2210115119, 2022 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-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.
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Base de dados:
MEDLINE
Assunto principal:
Vibrio cholerae
/
Proteína Receptora de AMP Cíclico
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article