Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor
[FSHR_HUMAN] Defects in FSHR are a cause of ovarian dysgenesis type 1 (ODG1) [MIM:233300]; also known as premature ovarian failure or gonadal dysgenesis XX type or XX gonadal dysgenesis (XXGD) or hereditary hypergonadotropic ovarian failure or hypergonadotropic ovarian dysgenesis with normal karyotype. ODG1 is an autosomal recessive disease characterized by primary amenorrhea, variable development of secondary sex characteristics, and high serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).       Defects in FSHR are a cause of ovarian hyperstimulation syndrome (OHSS) [MIM:608115]. OHSS is a disorder which occurs either spontaneously or most often as an iatrogenic complication of ovarian stimulation treatments for in vitro fertilization. The clinical manifestations vary from abdominal distention and discomfort to potentially life-threatening, massive ovarian enlargement and capillary leak with fluid sequestration. Pathologic features of this syndrome include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis.     [FSHB_HUMAN] Defects in FSHB are a cause of isolated follicle-stimulating hormone deficiency (IFSHD) [MIM:229070]. Selective follicle-stimulating hormone deficiency is an uncommon cause of infertility, producing amenorrhea and hypogonadism in women and oligo or azoospermia with normal testosterone levels in normally virilised men.  
[FSHR_HUMAN] Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. [FSHB_HUMAN] Stimulates development of follicle and spermatogenesis in the reproductive organs.
Publication Abstract from PubMed
FSH, a glycoprotein hormone, and the FSH receptor (FSHR), a G protein-coupled receptor, play central roles in human reproduction. We report the crystal structure of FSH in complex with the entire extracellular domain of FSHR (FSHR(ED)), including the enigmatic hinge region that is responsible for signal specificity. Surprisingly, the hinge region does not form a separate structural unit as widely anticipated but is part of the integral structure of FSHR(ED). In addition to the known hormone-binding site, FSHR(ED) provides interaction sites with the hormone: a sulfotyrosine (sTyr) site in the hinge region consistent with previous studies and a potential exosite resulting from putative receptor trimerization. Our structure, in comparison to others, suggests FSHR interacts with its ligand in two steps: ligand recruitment followed by sTyr recognition. FSH first binds to the high-affinity hormone-binding subdomain of FSHR and reshapes the ligand conformation to form a sTyr-binding pocket. FSHR then inserts its sTyr (i.e., sulfated Tyr335) into the FSH nascent pocket, eventually leading to receptor activation.
Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor.,Jiang X, Liu H, Chen X, Chen PH, Fischer D, Sriraman V, Yu HN, Arkinstall S, He X Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12491-6. Epub 2012 Jul 16. PMID:22802634
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.