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Updated: Jun 29, 2026
10:07
Identification of Post-translational Modifications of Plant Protein Complexes
Published on: February 22, 2014
Molecular basis for PKR activation by PACT or dsRNA
Shoudong Li1, Gregory A Peters, Keyang Ding
1Department of Molecular Genetics/NE20, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Summary
Protein kinase PKR (PKR) activation is key to antiviral immunity. This study reveals an intramolecular interaction keeps PKR inactive, and disrupting it activates the enzyme, suggesting a new activation model.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Protein kinase PKR (PKR) is vital for innate immunity against viral infections.
- PKR regulates cell signaling and translation, but its activation mechanism is unclear.
- PKR requires activators like dsRNA or PACT protein to become enzymatically active.
Purpose of the Study:
- To elucidate the molecular mechanism of PKR activation.
- To identify the interaction responsible for maintaining PKR in an inactive state.
Main Methods:
- Biochemical assays
- Genetic analyses
- Nuclear Magnetic Resonance (NMR) spectroscopy
Main Results:
- Identified the PACT-binding motif (PBM) within the PKR kinase domain.
- Demonstrated an intramolecular interaction between PBM and the dsRNA-binding domain, inhibiting PKR.
- Disrupting this interaction via point mutations or a decoy peptide led to constitutive PKR activation.
Conclusions:
- An intramolecular interaction maintains PKR in an inactive conformation.
- This interaction can be disrupted by PACT or dsRNA binding, leading to PKR activation.
- A model for PKR activation involving intramolecular inhibition is proposed.
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