PROTÉINES MUTANTES ET MÉTHODES DE PRODUCTION DE TELLES PROTÉINES

摘要

A method of producing a mutant GPCR with increased conformational stability under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, relative to its parent GPCR, the method comprising: (a) identifying in the amino acid sequence of one or more mutants of a first parent GPCR with increased conformational stability under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, relative to the first parent GPCR, the position or positions at which the one or more mutants have at least one different amino acid residue compared to the first parent GPCR, and (b) making one or more mutations in the amino acid sequence that defines a second GPCR within a window or windows of i plus or minus 5 residues where i is the corresponding position or positions, to provide one or more mutants of a second parent GPCR with increased conformational stability relative to the second parent GPCR; wherein the second GPCR is able to be aligned with the first GPCR and the corresponding position or positions are as identified by alignment.