The glycoprotein hormones: recent studies of structure‐function relationships

Abstract

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.

NMR Studies of the Free α Subunit of Human Chorionic Gonadotropin

“…ahCG concentration was 5 mM, the endo-B-treated ahCG concentration was different for different experiments and varied from 2.5 mM to 5 rnM, as determined by absorbance at 280 nm with a molar extinction coefficient of 6.4X10'M NMR spectroscopy. NMR spectra were recorded at 303, 308, 323, 328, or 338 K with Bruker AMX-500, Bruker AMXc m~-' (Ryan et al, 1988). 600 or Varian UnityPlus 750-MHz spectrometers (Bijvoet Center, Utrecht University and NSR Center, University of Nijmegen).…”

Effect of Site Directed Mutagenesis in the CMGCC Region of the .ALPHA.-Subunit on Immunoreactive Human Thyrotropin.

“…The amino acid sequences of a-subunits (common a-subunit) are identical in all glycoprotein hormones and those of f3-subunits are specific for each hormone. The structural relationships of glycoprotein hormones with their biological and immunological activities have been investigated by chemical and immunological techniques [1][2][3][4][5].…”

Molecular structures of glycoprotein hormones and functions of their carbohydrate components

“…This perception is based on the observations that the al-6 bond of di-or tri-antennary oligosaccharides is flexible [240][241][242][243][244][245][246] and that analytical centrifugation of native and deglycosylated hormones revealed essentially no difference in sedimentation constant [247].…”