Extracellular nanobody screening using conformationally stable GPCR variants

Proceedings of the National Academy of Sciences, Volume 122, Number 45, November 2025.
Significance We present a universal strategy to stabilize G protein-coupled receptors (GPCRs) in defined conformational states, overcoming the challenges posed by their intrinsic dynamics. Through de novo engineering of fusion proteins to lock in the M1 muscarinic system…