3T0Y

Structure of the PhyR anti-anti-sigma domain bound to the anti-sigma factor, NepR

Summary for 3T0Y

• Entry DOI: 10.2210/pdb3t0y/pdb
• Descriptor: Response regulator, NepR (3 entities in total)
• Functional Keywords: sigma factor, anti-sigma factor, receiver domain, gene regulation, signal transduction, transcription regulator-protein binding complex, transcription regulator/protein binding
• Biological source: Caulobacter vibrioides; More
• Total number of polymer chains: 4
• Total formula weight: 47227.32

Authors

Herrou, J.,Crosson, S. (deposition date: 2011-07-20, release date: 2012-05-02, Last modification date: 2024-11-20)

Primary citation

Herrou, J.,Rotskoff, G.,Luo, Y.,Roux, B.,Crosson, S.
Structural basis of a protein partner switch that regulates the general stress response of alpha-proteobacteria
Proc.Natl.Acad.Sci.USA, 109:E1415-E1423, 2012

PubMed Abstract: α-Proteobacteria uniquely integrate features of two-component signal transduction (TCS) and alternative sigma factor (σ) regulation to control transcription in response to general stress. The core of this regulatory system is the PhyR protein, which contains a σ-like (SL) domain and a TCS receiver domain. Aspartyl phosphorylation of the PhyR receiver in response to stress signals promotes binding of the anti-σ factor, NepR, to PhyR-SL. This mechanism, whereby NepR switches binding between its cognate σ factor and phospho-PhyR (PhyR∼P), controls transcription of the general stress regulon. We have defined the structural basis of the PhyR∼P/NepR interaction in Caulobacter crescentus and characterized the effect of aspartyl phosphorylation on PhyR structure by molecular dynamics simulations. Our data support a model in which phosphorylation of the PhyR receiver domain promotes its dissociation from the PhyR-SL domain, which exposes the NepR binding site. A highly dynamic loop-helix region (α3-α4) of the PhyR-SL domain plays an important role in PhyR∼P binding to NepR in vitro, and in stress-dependent activation of transcription in vivo. This study provides a foundation for understanding the protein-protein interactions and protein structural dynamics that underpin general stress adaptation in a large and metabolically diverse clade of the bacterial kingdom.

PubMed: 22550172
DOI: 10.1073/pnas.1116887109

Experimental method

X-RAY DIFFRACTION (2.102 Å)