CdbA is a DNA-binding protein and c-di-GMP receptor important for nucleoid organization and segregation in Myxococcus xanthus
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Cyclic di-GMP (c-di-GMP) is a second messenger that modulates multiple responses to environmental and cellular signals in bacteria. Here we identify CdbA, a DNA-binding protein of the ribbon-helix-helix family that binds c-di-GMP in Myxococcus xanthus. CdbA is essential for viability, and its depletion causes defects in chromosome organization and segregation leading to a block in cell division. The protein binds to the M. xanthus genome at multiple sites, with moderate sequence specificity; however, its depletion causes only modest changes in transcription. The interactions of CdbA with c-di-GMP and DNA appear to be mutually exclusive and residue substitutions in CdbA regions important for c-di-GMP binding abolish binding to both c-di-GMP and DNA, rendering these protein variants non-functional in vivo. We propose that CdbA acts as a nucleoid-associated protein that contributes to chromosome organization and is modulated by c-di-GMP, thus revealing a link between c-di-GMP signaling and chromosome biology.
Funding Information: We thank Jörg Kahnt for mass-spectrometry analysis, Dr. Nuria Gómez Santos for providing the plasmid pNG62, Prof. Dr. Anke Becker for helpful discussions and Max Planck Genome Centre Cologne (https://mpgc.mpipz.mpg.de/home) for ChIP-seq library construction and next-generation sequencing. This work was supported by funding from the Deutsche Forschungsgemeinschaft (DFG) within the framework of the Collaborative Research Center SFB987 “Microbial Diversity in Environmental Signal Response” (to L.S.-A.) and the priority programme SPP 1879 “Nucleotide Second Messenger Signaling in Bacteria” (to L.S.-A. and G.B.) and the Max Planck Society (to L.S.-A.). We acknowledge support by the Deutsche Forschungsgemeinschaft (DFG) through the DFG core facility for interactions, dynamics, and macromolecular assembly structure (to G.B.).
|Number of pages||19|
|Publication status||Published - 14 Apr 2020|
- Bacterial Proteins/chemistry, Base Sequence, Cell Nucleus/metabolism, Chromosome Segregation, Chromosomes, Bacterial/metabolism, Cyclic GMP/analogs & derivatives, DNA, Bacterial/metabolism, DNA-Binding Proteins/metabolism, Genetic Loci, Models, Molecular, Myxococcus xanthus/metabolism, Protein Multimerization, Protein Structure, Secondary, Transcription, Genetic