title: The specificity of binding of glycoprotein hormones to their receptors.
abstract: The glycoprotein hormone receptor family is peculiar because, in contrast to other G protein-coupled receptors, a large N-terminal extracellular ectodomain is responsible for hormone recognition. Hormone-receptor pairs have evolved in such a manner that a limited number of positions both at the 'seat-belt' domain of the hormone and the leucine-rich repeats of the receptor, play attractive and repulsive interactions for binding and specificity, respectively. Surprisingly, the constitutive activity of the receptor, mostly modulated by highly conserved amino acids within the heptahelical domain of the receptor (i.e., outside the hormone binding region), also regulates effectiveness of hormone recognition by the extracellular part. In this review we analyze, at the molecular level, these important discriminating determinants for selective binding of glycoprotein hormones to their receptors, as well as natural mutations, observed in patients with gestational hyperthyroidism or ovarian hyperstimulation syndrome, that modify the selectivity of binding.
authors.affiliation: Laboratori de Medicina Computacional, Unitat de Bioestadistica, Facultat de Medicina, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Caltabiano
authors.forename: M
authors.initials: M
authors.lastname: Campillo
authors.forename: A
authors.initials: A
authors.lastname: De Leener
authors.forename: G
authors.initials: G
authors.lastname: Smits
authors.forename: G
authors.initials: G
authors.lastname: Vassart
authors.forename: S
authors.initials: S
authors.lastname: Costagliola
authors.forename: L
authors.initials: L
authors.lastname: Pardo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006728:Hormones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D040681:Structural Homology, Protein
chemical_list: D006023:Glycoproteins; D006728:Hormones; D011956:Receptors, Cell Surface