Back to Search
Start Over
Regulation of signaling directionality revealed by 3D snapshots of a kinase:regulator complex in action
- Source :
- eLife, Vol 5 (2016), eLife, eLife, eLife Sciences Publication, 2016, 5, pp.e21422. ⟨10.7554/eLife.21422⟩, eLife, 2016, 5, pp.e21422. ⟨10.7554/eLife.21422⟩
- Publication Year :
- 2016
- Publisher :
- eLife Sciences Publications Ltd, 2016.
-
Abstract
- Two-component systems (TCS) are protein machineries that enable cells to respond to input signals. Histidine kinases (HK) are the sensory component, transferring information toward downstream response regulators (RR). HKs transfer phosphoryl groups to their specific RRs, but also dephosphorylate them, overall ensuring proper signaling. The mechanisms by which HKs discriminate between such disparate directions, are yet unknown. We now disclose crystal structures of the HK:RR complex DesK:DesR from Bacillus subtilis, comprising snapshots of the phosphotransfer and the dephosphorylation reactions. The HK dictates the reactional outcome through conformational rearrangements that include the reactive histidine. The phosphotransfer center is asymmetric, poised for dissociative nucleophilic substitution. The structural bases of HK phosphatase/phosphotransferase control are uncovered, and the unexpected discovery of a dissociative reactional center, sheds light on the evolution of TCS phosphotransfer reversibility. Our findings should be applicable to a broad range of signaling systems and instrumental in synthetic TCS rewiring. DOI: http://dx.doi.org/10.7554/eLife.21422.001
- Subjects :
- 0301 basic medicine
Models, Molecular
MESH: Signal Transduction
Histidine Kinase
Protein Conformation
Regulator
Crystallography, X-Ray
Phosphotransferase
MESH: Protein Conformation
biophysics
B. subtilis
Transferase
structural biology
Phosphorylation
Biology (General)
Microbiology and Infectious Disease
Kinase
General Neuroscience
General Medicine
MESH: Transcription Factors
Biophysics and Structural Biology
Cell biology
Biochemistry
MESH: Histidine Kinase
Medicine
phosphoryl-transfer mechanism
MESH: Models, Molecular
Research Article
Bacillus subtilis
Signal Transduction
Cell signaling
QH301-705.5
infectious disease
Science
Phosphatase
Biology
General Biochemistry, Genetics and Molecular Biology
Dephosphorylation
03 medical and health sciences
[CHIM.CRIS]Chemical Sciences/Cristallography
cell signaling
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
030102 biochemistry & molecular biology
General Immunology and Microbiology
MESH: Phosphorylation
microbiology
E. coli
MESH: Bacillus subtilis
MESH: Crystallography, X-Ray
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
030104 developmental biology
Structural biology
MESH: Protein Processing, Post-Translational
two component systems
Protein Processing, Post-Translational
Transcription Factors
allosteric control of protein function
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....94f50326360c2b6ecffe90612b0d66f5