4ZSK

Crystal structure of the effector-binding domain of DasR (DasR-EBD) in complex with N-acetylglucosamine-6-phosphate

Summary for 4ZSK

• Entry DOI: 10.2210/pdb4zsk/pdb
• Descriptor: HTH-type transcriptional repressor DasR, 2-acetamido-2-deoxy-6-O-phosphono-alpha-D-glucopyranose, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: transcription, repressor, bacterial transcription regulation, transcription factor, gntr/hutc family, effector-binding domain, n-acetylglucosamine utilization, master regulator, n-acetylglucosamine-6-phosphate
• Biological source: Streptomyces coelicolor A3(2)
• Cellular location: Cytoplasm : Q9K492
• Total number of polymer chains: 2
• Total formula weight: 39166.38

Authors

Fillenberg, S.B.,Muller, Y.A. (deposition date: 2015-05-13, release date: 2016-06-08, Last modification date: 2024-01-10)

Primary citation

Fillenberg, S.B.,Friess, M.D.,Korner, S.,Bockmann, R.A.,Muller, Y.A.
Crystal Structures of the Global Regulator DasR from Streptomyces coelicolor: Implications for the Allosteric Regulation of GntR/HutC Repressors.
Plos One, 11:e0157691-e0157691, 2016

PubMed 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.

PubMed: 27337024
DOI: 10.1371/journal.pone.0157691

Experimental method

X-RAY DIFFRACTION (1.85 Å)