The glycoprotein hormones: recent studies of structure-function relationships.
The structural features of the heterodimeric glycoprotein hormones (LH, FSH, TSH, and hCG) are briefly reviewed. Removal of carbohydrate chains does not reduce binding of the hormones to membrane receptors, but markedly reduces biological responses. The glycopeptides from the hormone do not reduce binding of native hormone to receptors but do reduce biological responses. Newer data concerned with replication of different regions of the peptide chains of these molecules using synthetic peptides are reviewed and presented. These studies indicate that two regions on the common alpha subunit are involved with receptor binding of the LH, hCG, and TSH molecules. These regions are alpha 26 to 46 and alpha 75-92. Two synthetic disulfide loop peptides from the hCG beta subunit beta 38-57 and beta 93-100 also block binding of hCG to its receptor. In addition, the beta 38-57 peptide stimulates testosterone production by Leydig cells. These data indicate that glycoprotein hormone binding to plasma membrane receptors involves a discontinuous site on the hormone that spans both the alpha and beta subunits, and that the alpha subunit sites are similar for several hormones.
Ryan
R J
RJ
Department of Biochemistry and Molecular Biology, Mayo Medical School, Rochester, Minnesota 55905.
Charlesworth
M C
MC
McCormick
D J
DJ
Milius
R P
RP
Keutmann
H T
HT
D000595:Amino Acid Sequence; D000818:Animals; D006063:Chorionic Gonadotropin / Q000235:genetics; D018997:Chorionic Gonadotropin, beta Subunit, Human; D006023:Glycoproteins / Q000502:physiology*; D006728:Hormones / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology; D013329:Structure-Activity Relationship
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D006023:Glycoproteins; D006728:Hormones; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011956:Receptors, Cell Surface