BusR senses bipartite DNA binding motifs by a unique molecular ruler architecture.
ATP-Binding Cassette Transporters
/ genetics
Biological Transport
/ genetics
Crystallography, X-Ray
DNA, Bacterial
/ genetics
DNA-Binding Proteins
/ genetics
Dinucleoside Phosphates
/ metabolism
Gene Expression Regulation, Bacterial
/ genetics
Potassium
/ metabolism
Protein Domains
/ genetics
Second Messenger Systems
/ genetics
Streptococcus agalactiae
/ genetics
Transcription Factors
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
27 09 2021
27 09 2021
Historique:
accepted:
12
08
2021
revised:
27
07
2021
received:
24
02
2021
pubmed:
26
8
2021
medline:
21
12
2021
entrez:
25
8
2021
Statut:
ppublish
Résumé
The cyclic dinucleotide second messenger c-di-AMP is a major player in regulation of potassium homeostasis and osmolyte transport in a variety of bacteria. Along with various direct interactions with proteins such as potassium channels, the second messenger also specifically binds to transcription factors, thereby altering the processes in the cell on the transcriptional level. We here describe the structural and biochemical characterization of BusR from the human pathogen Streptococcus agalactiae. BusR is a member of a yet structurally uncharacterized subfamily of the GntR family of transcription factors that downregulates transcription of the genes for the BusA (OpuA) glycine-betaine transporter upon c-di-AMP binding. We report crystal structures of full-length BusR, its apo and c-di-AMP bound effector domain, as well as cryo-EM structures of BusR bound to its operator DNA. Our structural data, supported by biochemical and biophysical data, reveal that BusR utilizes a unique domain assembly with a tetrameric coiled-coil in between the binding platforms, serving as a molecular ruler to specifically recognize a 22 bp separated bipartite binding motif. Binding of c-di-AMP to BusR induces a shift in equilibrium from an inactivated towards an activated state that allows BusR to bind the target DNA, leading to transcriptional repression.
Identifiants
pubmed: 34432045
pii: 6357733
doi: 10.1093/nar/gkab736
pmc: PMC8517857
doi:
Substances chimiques
ATP-Binding Cassette Transporters
0
DNA, Bacterial
0
DNA-Binding Proteins
0
Dinucleoside Phosphates
0
Transcription Factors
0
cyclic diadenosine phosphate
0
Potassium
RWP5GA015D
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10166-10177Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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