What is it about?
KARRIKIN INSENSITIVE 2 (KAI2) was initially identified as a protein that binds to karrikins, germination-inducing compounds in wildfire smoke. However, its endogenous ligand within plants (KAI2 ligand; KL) remains elusive. Recent studies have elucidated key aspects of KAI2 signaling mechanisms, yet the precise ligand recognition process remains largely unresolved. This study aimed to dissect the structural requirements of the KAI2 ligand and elucidate the molecular mechanism underlying KAI2 activation. To achieve this, we introduced structural modifications to the known KAI2 agonist, dMGer, to develop analogs that resist hydrolysis by KAI2. The binding affinity of these analogs (1'-carba-dMGer and 6'-carba-dMGer) to KAI2, as well as their physiological effects on plants, was thoroughly evaluated. Our results demonstrate that mere ligand binding to KAI2 is insufficient for signal transduction and that ligand hydrolysis and subsequent covalent adduct formation with the catalytic residues of KAI2 is a critical step for KAI2 activation. These findings will aid in identifying the endogenous KL molecule.
Featured Image
Photo by Ayush Kumar on Unsplash
Why is it important?
Recent genetic studies have suggested that ligand hydrolysis by KAI2 is a prerequisite for signaling, but direct experimental evidence has been lacking. Our study provides experimental data from a ligand structure–activity study that ligand hydrolysis plays a key role in KAI2 activation. This study highlights the usefulness of chemical tools in elucidating the action mechanisms of bioactive compounds, including in the field of plant science.
Perspectives
These results provide new insights into the structural features of KL, which has been undiscovered for more than a decade and should lead to the identification of KL as a new plant hormone candidate. For me, this study reaffirms the usefulness of chemical tools in plant science. The observations gained from this work pave the way for the rational design of KAI2-specific agonists (activators) and antagonists (inhibitors), enabling artificial regulation of KAI2 activity.
Jun Takeuchi
Shizuoka Daigaku
Read the Original
This page is a summary of: Structural requirements of KAI2 ligands for activation of signal transduction, Proceedings of the National Academy of Sciences, February 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2414779122.
You can read the full text:
Contributors
The following have contributed to this page
