Chimeric polypeptides comprising G protein-coupled receptors and VHH antibodies

Described are polypeptides and their use for screening and drug discovery. More specifically, the disclosure 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 the membrane protein. In particular, the chimeric polypeptides 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 screening methods for compounds using the chimeric polypeptides.