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 journalArticle

7 Citations (Scopus)

Abstract

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
Volume44
Issue number19
DOIs
Publication statusPublished - 2016 Nov 2

Fingerprint

Transcription
Guanosine Triphosphate
Branched Chain Amino Acids
Isoleucine
Binding Sites
Metabolites
Bacillus cereus
Electrophoretic mobility
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Hinges
Metabolism
Staphylococcus aureus
Assays
Genes
Crystal structure
Molecules
Sensors

ASJC Scopus subject areas

  • Genetics

Cite this

The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism. / Han, Ah Reum; Kang, Hye Ri; Son, Jonghyeon; Kwon, Do Hoon; Kim, Sulhee; Lee, Woo Cheol; Song, Hyun Kyu; Song, Moon Jung; Hwang, Kwang Yeon.

In: Nucleic Acids Research, Vol. 44, No. 19, 02.11.2016, p. 9483-9493.

Research output: Contribution to journalArticle

Han, Ah Reum ; Kang, Hye Ri ; Son, Jonghyeon ; Kwon, Do Hoon ; Kim, Sulhee ; Lee, Woo Cheol ; Song, Hyun Kyu ; Song, Moon Jung ; Hwang, Kwang Yeon. / The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism. In: Nucleic Acids Research. 2016 ; Vol. 44, No. 19. pp. 9483-9493.
@article{eb83d9b17dc541bfadb48eebad72964d,
title = "The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism",
abstract = "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.",
author = "Han, {Ah Reum} and Kang, {Hye Ri} and Jonghyeon Son and Kwon, {Do Hoon} and Sulhee Kim and Lee, {Woo Cheol} and Song, {Hyun Kyu} and Song, {Moon Jung} and Hwang, {Kwang Yeon}",
year = "2016",
month = "11",
day = "2",
doi = "10.1093/nar/gkw775",
language = "English",
volume = "44",
pages = "9483--9493",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "19",

}

TY - JOUR

T1 - The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism

AU - Han, Ah Reum

AU - Kang, Hye Ri

AU - Son, Jonghyeon

AU - Kwon, Do Hoon

AU - Kim, Sulhee

AU - Lee, Woo Cheol

AU - Song, Hyun Kyu

AU - Song, Moon Jung

AU - Hwang, Kwang Yeon

PY - 2016/11/2

Y1 - 2016/11/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84994607537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994607537&partnerID=8YFLogxK

U2 - 10.1093/nar/gkw775

DO - 10.1093/nar/gkw775

M3 - Article

VL - 44

SP - 9483

EP - 9493

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 19

ER -