TY - JOUR
T1 - The effects of synthetic α-subunit peptides on thyrotropin interaction with its receptor
AU - Morris, John C.
AU - Jiang, Nai Siang
AU - Charlesworth, M. Cristine
AU - Mcccormick, Daniel J.
AU - Ryan, Robert J.
PY - 1988/7/1
Y1 - 1988/7/1
N2 - Synthetic peptides of the α-subunit of human glycoprotein hormones have been shown previously to inhibit binding of [125I]iodo-hCG to ovarian membranes, thus indicating the importance of the α-subunit in the structure-function relationships of the gonadotropic hormone. These same synthetic α-subunit peptides, the sequences of which are common to all human glycoprotein hormones, were found to inhibit the binding of [126I]iodo-TSH to human thyroid membrane preparations and FRTL-5 rat thyroid cells. The active portions of the subunit were represented in synthetic peptides α21†35, α31†45, α26†46, and α81†92, indicating that 2 separate sites within the α-subunit have binding activity for TSH. Peptides α26†46 and α31†45 were also found to potently inhibit the stimulation of adenylate cyclase activity by bovine TSH in TSH bioassay using FRTL-5 cells. Seven other synthetic peptides, including the remainder of the 92-amino acid sequence of the α-subunit, demonstrated little or no ability to inhibit binding of the tracer or inhibit the bioactivity of intact TSH. The findings were very similar to those of previous studies involving hCG binding, except that the two active sites appeared to be somewhat shifted towards the COOH-terminal end of the subunit. These studies support the concept of the importance of the α-subunit in receptor binding of all glycoprotein hormones and demonstrate the utility of the overlapping synthetic peptide strategy in investigations of protein structure-function relationships.
AB - Synthetic peptides of the α-subunit of human glycoprotein hormones have been shown previously to inhibit binding of [125I]iodo-hCG to ovarian membranes, thus indicating the importance of the α-subunit in the structure-function relationships of the gonadotropic hormone. These same synthetic α-subunit peptides, the sequences of which are common to all human glycoprotein hormones, were found to inhibit the binding of [126I]iodo-TSH to human thyroid membrane preparations and FRTL-5 rat thyroid cells. The active portions of the subunit were represented in synthetic peptides α21†35, α31†45, α26†46, and α81†92, indicating that 2 separate sites within the α-subunit have binding activity for TSH. Peptides α26†46 and α31†45 were also found to potently inhibit the stimulation of adenylate cyclase activity by bovine TSH in TSH bioassay using FRTL-5 cells. Seven other synthetic peptides, including the remainder of the 92-amino acid sequence of the α-subunit, demonstrated little or no ability to inhibit binding of the tracer or inhibit the bioactivity of intact TSH. The findings were very similar to those of previous studies involving hCG binding, except that the two active sites appeared to be somewhat shifted towards the COOH-terminal end of the subunit. These studies support the concept of the importance of the α-subunit in receptor binding of all glycoprotein hormones and demonstrate the utility of the overlapping synthetic peptide strategy in investigations of protein structure-function relationships.
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U2 - 10.1210/endo-123-1-456
DO - 10.1210/endo-123-1-456
M3 - Article
C2 - 3383781
AN - SCOPUS:0023749683
SN - 0013-7227
VL - 123
SP - 456
EP - 462
JO - Endocrinology
JF - Endocrinology
IS - 1
ER -