How Cofactors Control the Activity of Ire1
Author Information
Author(s): Korennykh Alexei V, Egea Pascal F, Korostelev Andrei A, Finer-Moore Janet, Stroud Robert M, Zhang Chao, Shokat Kevan M, Walter Peter
Primary Institution: Howard Hughes Medical Institute, University of California, San Francisco
Hypothesis
The study investigates how the binding of cofactors to the kinase domain of Ire1 modulates its RNase activity.
Conclusion
Cofactor-induced conformational changes in Ire1 are coupled to its oligomerization, which activates its RNase activity.
Supporting Evidence
- The kinase domain of Ire1 binds cofactors without activating the RNase domain.
- ADPβS binds to Ire1 but does not activate RNase, while Mn2+ can rescue RNase activity.
- Mutagenesis of the kinase domain suggests that conformational changes are crucial for RNase activation.
- X-ray crystallography shows that oligomerization of Ire1 can occur without cofactors.
Takeaway
Ire1 is a protein that helps cells respond to stress, and this study shows that certain molecules can change its shape and make it work better.
Methodology
The study used biochemical assays, mutagenesis, and X-ray crystallography to analyze Ire1's activity and structure.
Digital Object Identifier (DOI)
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