MUTANT G-PROTEIN COUPLED RECEPTORS WITH INCREASED CONFORMATIONAL STABILITY AND METHODS FOR PRODUCING THEM

摘要

A method of producing a mutant G-protein coupled receptor (GPCR) withincreased stability relative to its parentGPCR, the method comprising: a) providing one or more mutants of a firstparent GPCR with increased stability relative to the firstparent GPCR b) identifying in a structural membrane protein model thestructural motif or motifs in which the one or more mutantshave at least one different amino acid residue compared to the first parentGPCR, and c) making one or more mutations in the aminoacid sequence that defines a corresponding structural motif or motifs in asecond parent GPCR, to provide one or more mutants ofa second parent GPCR with increased stability relative to the second parentGPCR. Mutants of .beta.-adrenergic receptor, adenosinereceptor and neurotensin receptor are also disclosed.