Mutant proteins and methods for selecting them

摘要

A method for selecting a G-protein coupled receptor (GPCR) with increased stability, the method comprising (a) providing one or more mutants of a parent GPCR, (b) selecting a ligand, the ligand being one which binds to the parent GPCR when the GPCR is residing in a particular conformation, 5 (c) determining whether the or each mutant GPCR has increased stability with respect to binding the selected ligand compared to the stability of the parent GPCR with respect to binding that ligand, and (d) selecting those mutants that have an increased stability compared to the parent GPCR with respect to binding the selected ligand. Mutants of p-adrenergic receptor, adenosine receptor and neurotensin receptor are also disclosed.