4ZSI

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

4ZSI の概要

• エントリーDOI: 10.2210/pdb4zsi/pdb
• 分子名称: HTH-type transcriptional repressor DasR, 2-amino-2-deoxy-6-O-phosphono-alpha-D-glucopyranose, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: transcription, repressor, bacterial transcription regulation, transcription factor, gntr/hutc family, effector-binding domain, n-acetylglucosamine utilization, master regulator, glucosamine-6-phosphate
• 由来する生物種: Streptomyces coelicolor A3(2)
• 細胞内の位置: Cytoplasm : Q9K492
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38958.17

構造登録者

Fillenberg, S.B.,Koerner, S.,Muller, Y.A. (登録日: 2015-05-13, 公開日: 2016-06-08, 最終更新日: 2024-01-10)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.652 Å)