Towards understanding the glycoprotein hormone receptors.
Lutropin (LH), follitropin (FSH) and thyrotropin (TSH), as well as choriogonadotropin (CG, which binds to the LH receptor) constitute the glycoprotein hormone family. Their 3 receptors have been cloned during the last few months. They belong to the large group of G-protein coupled membrane proteins, with their specific N-terminal domain likely to bind the hormone and the characteristic 7 membrane-spanning segments in their C-terminal moiety. The present review discusses the main results of amino acid sequence analysis performed on the glycoprotein hormone receptors. The putative extracellular head exhibits less than 45% homology over the 3 receptors, while approximately 70% residue conservation is found in the transmembrane moiety. Here only, limited sequence homologies (approximately 20%) can be found with other G-protein coupled receptors. The secondary structure predictions performed on the 3 receptors revealed that the polypeptide sequence predicted as ordered (either alpha-helix or beta-strand) were repeated evenly throughout the extracellular head with a period of approximately 25 amino acids. This analysis helped to define the intervening loops between this ordered stretches as potential candidates for bearing at least part of the binding site of the hormones. Some of the perspectives opened by the cloning of the receptors are described, like the production of the extracellular head of the porcine LH receptor in baculovirus-infected insect cells, and the exploration of the LH receptor's mechanism of functioning as a dimer.
Salesse
R
R
Unité d'Ingénierie des Protéines, INRA-Biotechnologies, Jouy-en-Josas, France.
Remy
J J
JJ
Levin
J M
JM
Jallal
B
B
Garnier
J
J
D000595:Amino Acid Sequence; D001665:Binding Sites; D006023:Glycoproteins / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism; D011962:Receptors, FSH / Q000737:chemistry* / Q000378:metabolism; D011967:Receptors, Gonadotropin / Q000737:chemistry* / Q000378:metabolism; D011974:Receptors, LH / Q000737:chemistry* / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment
D006023:Glycoproteins; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D011962:Receptors, FSH; D011967:Receptors, Gonadotropin; D011974:Receptors, LH; D011989:Receptors, Thyrotropin