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Engineered chemotaxis core signaling units indicate a constrained kinase-off state
Alise R Muok1,2, Teck Khiang Chua1, Madhur Srivastava1,3
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Science Signaling
|November 11, 2020
Summary
Engineered bacterial chemoreceptor signaling units form stable, inhibited complexes. This reveals how chemoreceptors control histidine kinase (CheA) activity, preventing unwanted signaling.
Area of Science:
- Molecular Biology
- Biochemistry
- Microbiology
Background:
- Bacterial chemoreceptors, CheA, and CheW form signaling arrays controlling cellular responses.
- Receptor activity modulates CheA kinase activity based on environmental signals (attractants/repellants).
Purpose of the Study:
- To engineer and characterize stable mimics of bacterial chemosensory signaling units.
- To elucidate the structural basis of the inhibited (kinase-off) state in chemoreceptor arrays.
Main Methods:
- Site-directed spin-labeling with pulse-dipolar electron-spin resonance spectroscopy (PDS).
- Small-angle X-ray scattering (SAXS).
- Protein cross-linking and cryo-electron microscopy (cryo-EM).
Main Results:
- Engineered chemoreceptor regions formed stable trimers of receptor dimers complexed with CheA and CheW.
- These complexes adopted a stable kinase-off state with reduced domain mobility.
- The inhibited state sequesters kinase and substrate domains, preventing CheA autophosphorylation.
Conclusions:
- Provides a structurally restrained model for the inhibited state of the core chemosensory signaling unit.
- Demonstrates indirect sequestration of CheA domains by chemoreceptors limits kinase activity.
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