How the vasopressin receptor folds and how drugs can stabilize it in diabetes insipidus
Single-molecule Measurements of Membrane-protein Folding and Ligand-Interaction Energetics in Bacteriorhodopsin and the Diabetes-insipidus-involved Vasopressin Receptor 2
This work looks at how the vasopressin receptor folds and how binding drugs change its stability, with relevance for people who have nephrogenic diabetes insipidus.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Clemson University NIH-funded |
| Lab location | 1 site (Clemson, United States) |
| Project ID | NIH-11177924 on NIH RePORTER |
What this research studies
This project uses single-molecule biophysics to measure how the human vasopressin receptor (AVPR2) folds and unfolds and how small-molecule drugs called vaptans alter those folding energies. Researchers will examine disease-linked AVPR2 mutations known to cause nephrogenic diabetes insipidus and compare their folding behavior to the normal receptor. Experiments use high-resolution tools such as atomic force microscopy and precise energy measurements to track folding and ligand interactions at the molecular level. The goal is to reveal how misfolding causes loss of receptor function and how drugs can act like chaperones to restore the receptor's proper shape.
Who could benefit from this research
Good fit: People with nephrogenic diabetes insipidus caused by mutations in the AVPR2 gene would be the most relevant group for the implications of this work.
Not a fit: People with central diabetes insipidus or kidney problems not caused by AVPR2 mutations are unlikely to benefit directly from the specific findings.
Why it matters
Potential benefit: If successful, the findings could guide development of better therapies that restore AVPR2 function for people with nephrogenic diabetes insipidus and inform treatments for other GPCR misfolding diseases.
How similar studies have performed: Prior cell-based studies have shown that vaptan drugs can rescue cell-surface expression of some mutant AVPR2 receptors, but applying single-molecule energetic measurements to AVPR2 is a novel approach.
Where this research is happening
Clemson, United States
- Clemson University — Clemson, United States (Active)
Researchers
- Principal investigator: Jacobson, David R — Clemson University
- Study coordinator: Jacobson, David R
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.