Abstract: The present invention relates in some aspects to mutant G protein coupled receptors (GPCRs) and methods for selecting those with increased stability. In certain aspects, the invention relates to the selection and preparation of mutant GPCRs which have increased stability under a particular condition compared to their respective parent proteins.

Abstract: Aspects of the invention relate to methods of producing a mutant GPCR with increased stability relative to its parent GPCR.

Abstract: A method for producing a mutant G-protein coupled receptor (GPCR) with increased stability relative to a parent GPCR, the method comprising making one or more mutations in the amino acid sequence that defines a parent GPCR, wherein (i) the one or more mutations are located within a window of/plus or minus 5 residues, where/is the position of amino acid residue 2.46 in the parent GPCR when the parent GPCR is a Class 1 GPCR, or where/is the position of an equivalent amino acid residue in the parent GPCR when the parent GPCR is a Class 2 or 3 GPCR, and/or (ii) the one or more mutations are located within an amino acid sequence of transmembrane helix 7 in the parent GPCR which amino acid sequence interacts with the window of/plus or minus 5 residues, to provide one or more mutants of the parent GPCR with increased stability.

Abstract: The invention relates to mutant G-protein coupled receptors with increased conformational stability, and methods of use thereof. In some aspects, polynucleotides encoding the mutant G-protein coupled receptors are provided. In some aspects, host cells comprising the polynucleotides are provided. In some aspects, the invention relates to crystallized forms of the mutant G-protein coupled receptors, and methods of preparing the same.

Abstract: The invention provides a method of predicting a three dimensional structural representation of a target protein of unknown structure, or part thereof, comprising: providing the coordinates of the turkey ?1-AR structure listed in Table A, Table B, Table C or Table D, optionally varied by a root mean square deviation of residue backbone atoms of not more than 1.235 A, or selected coordinates thereof; and predicting the three-dimensional structural representation of the target protein, or part thereof, by modelling the structural representation on all or the selected coordinates of the turkey ?1-AR. The invention also provides the use of the turkey ?1-AR coordinates to select or design one or more binding partners of ?1-AR.

Abstract: A method for selecting a membrane protein with increased stability, the method comprising: a) providing one or more mutants of a parent membrane protein in a membrane-containing composition, wherein the one or more mutants are exposed to an amount of a membrane destabilising agent which is effective to destabilise the parent membrane protein in-situ, b) determining whether the or each mutant membrane protein has increased stability with respect to its structure and/or a biological activity compared to the stability of the parent membrane protein with respect to its structure and/or the same biological activity, and c) selecting the one or more mutants which have increased stability compared to the stability of the parent membrane protein.

Abstract: 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 hinds to the parent GPCR when the GPCR is residing in a particular conformation, (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 ?-adrenergic receptor, adenosine receptor and neurotensin receptor are also disclosed.