By the same authors

From the same journal

From the same journal

Structure of the Branched Chain Amino Acid and GTP Sensing Global Regulator, CodY, from Bacillus subtilis

Research output: Contribution to journalArticlepeer-review

Full text download(s)

Published copy (DOI)



Publication details

JournalThe Journal of biological chemistry
DateAccepted/In press - 23 Dec 2016
DateE-pub ahead of print (current) - 23 Dec 2016
Number of pages36
Pages (from-to)1-36
Early online date23/12/16
Original languageEnglish


CodY is a branched-chain amino acid (BCAA) and GTP sensor, and a global regulator of transcription in low G + C Gram-positive bacteria. It controls the expression of over 100 genes and operons, principally by repressing during growth genes whose products are required for adaptations to nutrient limitation. CodY consists of a GAF domain that binds BCAAs and a winged helix-turn-helix (wHTH) domain that binds to DNA, but the way in which these domains interact and the structural basis of the BCAA-dependence of this interaction are unknown. To gain new insights, we determined the crystal structure of unliganded CodY from Bacillus subtilis revealing a 10-turn alpha-helix linking otherwise discrete GAF and wHTH domains. The structure of CodY in complex with isoleucine revealed a reorganised GAF domain. In both complexes CodY was tetrameric. Size exclusion chromatography with multiangle laser light scattering (SEC-MALLS) experiments showed that CodY is a dimer at concentrations found in bacterial cells. Comparison of structures of dimers of unliganded CodY and CodY-Ile derived from the tetramers showed a splaying of the wHTH domains when Ile was bound; splaying is likely to account for the increased affinity of Ile-bound CodY for DNA. Electrophoretic mobility shift and SEC-MALLS analyses of CodY binding to 19-36 base-pair operator fragment are consistent with isoleucine-dependent binding of two CodY dimers per duplex. The implications of these observations for effector control of CodY activity are discussed.

Bibliographical note

Copyright 2016 by The American Society for Biochemistry and Molecular Biology, Inc. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.


Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations