3T0Y: Structure Of The Phyr Anti-Anti-Sigma Domain Bound To The Anti-Sigma Factor, Nepr

alpha-Proteobacteria uniquely integrate features of two-component signal transduction (TCS) and alternative sigma factor (sigma) regulation to control transcription in response to general stress. The core of this regulatory system is the PhyR protein, which contains a sigma-like (SL) domain and a TCS receiver domain. Aspartyl phosphorylation of the PhyR receiver in response to stress signals promotes binding of the anti-sigma factor, NepR, to PhyR-SL. This mechanism, whereby NepR switches binding between its cognate sigma factor and phospho-PhyR (PhyR approximately P), controls transcription of the general stress regulon. We have defined the structural basis of the PhyR approximately 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 (alpha3-alpha4) of the PhyR-SL domain plays an important role in PhyR approximately 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.
PDB ID: 3T0YDownload
MMDB ID: 99170
PDB Deposition Date: 2011/7/20
Updated in MMDB: 2012/06
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 3T0Y: tetrameric; determined by author and by software (PISA)
Molecular Components in 3T0Y
Label Count Molecule
Proteins (4 molecules)
Response Regulator
Molecule annotation
Molecule annotation
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Citing MMDB