Accessibility of the extracellular loops of follicle stimulating hormone receptor and their role in hormone–receptor interaction

The follicle stimulating hormone receptor (FSHR), a member of the G-protein coupled receptor family, has a large extracellular domain (ECD) which is responsible for hormone binding specificity. Whether the extracellular loops (ELs) of FSHR which are outward projections of its transmembrane domain have any role in receptor function is not yet well understood. Here, we use antipeptide antibodies to peptides corresponding to the FSHR-ELs to check the surface accessibility of the loops. These antibodies were further used to understand the involvement of the loops in hormone binding and signaling. The results demonstrate that EL1 and EL3 are surface accessible on the mature receptor in spite of the presence of a large ECD. It is observed that the EL1 and EL3 serve as secondary binding sites and they possibly interact with the ECD-bound hormone's α subunit which is common to the gonadotropins.