Novel chimeric polypeptides for screening and drug discovery purposes

The present invention relates to novel polypeptides and their use for screening and drug discovery. More specifically, the invention provides chimeric polypeptides comprising a membrane protein, in particular a GPCR, fused to a binding domain, wherein the binding domain is directed against and/or specifically binds to said membrane protein. In particular, the chimeric polypeptides of the invention are single proteins wherein, in an intramolecular reaction, the binding domain stabilizes the membrane protein in a conformation of interest. Also provided are nucleic acid sequences encoding such chimeric polypeptides, cells capable of expressing such chimeric polypeptides as well as cellular compositions derived thereof. Also envisaged are screening methods for compounds using the chimeric polypeptides of the invention.