Structural highlights
Function
[CODY_BACCR] DNA-binding protein that represses the expression of many genes that are induced as cells make the transition from rapid exponential growth to stationary phase. It is a GTP-binding protein that senses the intracellular GTP concentration as an indicator of nutritional limitations. At low GTP concentration it no longer binds GTP and stop to act as a transcriptional repressor.
Publication Abstract from PubMed
GTP and branched-chain amino acids (BCAAs) are metabolic sensors that are indispensable for the determination of the metabolic status of cells. However, their molecular sensing mechanism remains unclear. CodY is a unique global transcription regulator that recognizes GTP and BCAAs as specific signals and affects expression of more than 100 genes associated with metabolism. Herein, we report the first crystal structures of the full-length CodY complex with sensing molecules and describe their functional states. We observed two different oligomeric states of CodY: a dimeric complex of CodY from Staphylococcus aureus with the two metabolites GTP and isoleucine, and a tetrameric form (apo) of CodY from Bacillus cereus Notably, the tetrameric state shows in an auto-inhibitory manner by blocking the GTP-binding site, whereas the binding sites of GTP and isoleucine are clearly visible in the dimeric state. The GTP is located at a hinge site between the long helical region and the metabolite-binding site. Together, data from structural and electrophoretic mobility shift assay analyses improve understanding of how CodY senses GTP and operates as a DNA-binding protein and a pleiotropic transcription regulator.
The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism.,Han AR, Kang HR, Son J, Kwon DH, Kim S, Lee WC, Song HK, Song MJ, Hwang KY Nucleic Acids Res. 2016 Sep 4. pii: gkw775. PMID:27596595[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Han AR, Kang HR, Son J, Kwon DH, Kim S, Lee WC, Song HK, Song MJ, Hwang KY. The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism. Nucleic Acids Res. 2016 Sep 4. pii: gkw775. PMID:27596595 doi:http://dx.doi.org/10.1093/nar/gkw775
