Phosphoinositides and inositol phosphates as molecular glues
Aleshia Seaton-Terry1, Alexander J Cutright1, Mong Na Claire Loi1,2
1Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
FEBS Letters
|June 19, 2026
Summary
Inositol phosphates (IPs) and phosphoinositide lipids (PIPs) act as molecular glues, mediating protein-protein interactions at interfaces. Further structural studies are needed to fully understand their roles in cellular regulation.
Area of Science:
- Molecular Biology
- Structural Biology
- Cellular Signaling
Background:
- Inositol phosphates (IPs) and phosphoinositide lipids (PIPs) are vital regulatory molecules in eukaryotic cells.
- While membrane PIPs recruit signaling proteins and IPs act as structural cofactors, recent evidence suggests novel roles.
Purpose of the Study:
- To review structural biology findings on how IPs and PIPs mediate protein-protein interactions.
- To highlight the under-appreciated role of IPs and PIPs at protein interfaces.
Main Methods:
- Review of recent structural biology studies.
- Analysis of protein-protein interactions mediated by IPs and PIPs.
Main Results:
- IPs and PIPs function as natural molecular glues at protein interfaces.
- Some protein-protein interactions mediated by IPs and PIPs require further high-resolution structural analysis.
Conclusions:
- IPs and PIPs play a significant, yet under-appreciated, role in mediating protein-protein interactions.
- A systematic, structural approach is necessary to fully elucidate these roles.
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