Crystal Structures of the Global Regulator DasR from Streptomyces coelicolor: Implications for the Allosteric Regulation of GntR/HutC Repressors.

Fillenberg S, Frieß M, Körner S, Böckmann R, Muller Y (2016)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2016

Journal

PLoS ONE Public Library of Science

Publisher: Public Library of Science

Book Volume: 11

Pages Range: e0157691

Journal Issue: 6

DOI: 10.1371/journal.pone.0157691

Abstract

Small molecule effectors regulate gene transcription in bacteria by altering the DNA-binding affinities of specific repressor proteins. Although the GntR proteins represent a large family of bacterial repressors, only little is known about the allosteric mechanism that enables their function. DasR from Streptomyces coelicolor belongs to the GntR/HutC subfamily and specifically recognises operators termed DasR-responsive elements (dre-sites). Its DNA-binding properties are modulated by phosphorylated sugars. Here, we present several crystal structures of DasR, namely of dimeric full-length DasR in the absence of any effector and of only the effector-binding domain (EBD) of DasR without effector or in complex with glucosamine-6-phosphate (GlcN-6-P) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P). Together with molecular dynamics (MD) simulations and a comparison with other GntR/HutC family members these data allowed for a structural characterisation of the different functional states of DasR. Allostery in DasR and possibly in many other GntR/HutC family members is best described by a conformational selection model. In ligand-free DasR, an increased flexibility in the EBDs enables the attached DNA-binding domains (DBD) to sample a variety of different orientations and among these also a DNA-binding competent conformation. Effector binding to the EBDs of DasR significantly reorganises the atomic structure of the latter. However, rather than locking the orientation of the DBDs, the effector-induced formation of β-strand β* in the DBD-EBD-linker segment merely appears to take the DBDs 'on a shorter leash' thereby impeding the 'downwards' positioning of the DBDs that is necessary for a concerted binding of two DBDs of DasR to operator DNA.

Authors with CRIS profile

Simon Fillenberg Lehrstuhl für Biotechnik (Proteinstruktur und -design) Mario Frieß Professur für Computational Biology Rainer Böckmann Professur für Computational Biology Yves Muller Lehrstuhl für Biotechnik (Proteinstruktur und -design)

Involved external institutions

Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Fillenberg, S., Frieß, M., Körner, S., Böckmann, R., & Muller, Y. (2016). Crystal Structures of the Global Regulator DasR from Streptomyces coelicolor: Implications for the Allosteric Regulation of GntR/HutC Repressors. PLoS ONE, 11(6), e0157691. https://dx.doi.org/10.1371/journal.pone.0157691

MLA:

Fillenberg, Simon, et al. "Crystal Structures of the Global Regulator DasR from Streptomyces coelicolor: Implications for the Allosteric Regulation of GntR/HutC Repressors." PLoS ONE 11.6 (2016): e0157691.

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