Single chain variants of the glycoprotein hormones and their receptors as tools to study receptor activation and for analogue design

One of the crucial steps in the biosynthesis of multisubunit proteins is their assembly. The glycoprotein hormone, thyroid-stimulating hormone, and the gonadotropins, luteinizing hormone, follicle-stimulating hormone and chorionic gonadotropin, are noncovalent heterodimers. Their assembly is critical for bioactivity because the heterodimers, but not the monomeric subunits, efficiently bind to and activate the cognate heptahelical receptor. Occasionally, mutated subunits cannot combine into a functional hormone, or the bioactivity of the assembled, yet modified, heterodimer is suboptimal.