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The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors

Townsend, P.; Jungwirth, B.; Pojer, P.; Bußmann, M.; Money, V.A.; Cole, S.T.; Pühler, A.; Tauch, A.; Bott, M.; Cann, M.J.; Pohl, E.

The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors Thumbnail


Authors

P. Townsend

B. Jungwirth

P. Pojer

M. Bußmann

V.A. Money

S.T. Cole

A. Pühler

A. Tauch

M. Bott



Abstract

The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator) transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition.

Citation

Townsend, P., Jungwirth, B., Pojer, P., Bußmann, M., Money, V., Cole, S., …Pohl, E. (2014). The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors. PLoS ONE, 9(12), Article e113265. https://doi.org/10.1371/journal.pone.0113265

Journal Article Type Article
Acceptance Date Oct 16, 2014
Online Publication Date Dec 3, 2014
Publication Date Dec 3, 2014
Deposit Date Oct 28, 2014
Publicly Available Date Mar 29, 2024
Journal PLoS ONE
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 12
Article Number e113265
DOI https://doi.org/10.1371/journal.pone.0113265

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Copyright: © 2014 Townsend et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.





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