The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism

Ah Reum Han, Hye Ri Kang, Jonghyeon Son, Do Hoon Kwon, Sulhee Kim, Woo Cheol Lee, Hyun Kyu Song, Moon Jung Song, Kwang Yeon Hwang

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)9483-9493
Number of pages11
JournalNucleic acids research
Issue number19
Publication statusPublished - 2016 Nov 2

Bibliographical note

Publisher Copyright:
© 2016 The Author(s).

ASJC Scopus subject areas

  • Genetics


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