Site-Directed Mutagenesis of Amino Acids 33-44 of the Common α-Subunit Reveals Different Structural Requirements for Heterodimer Expression among the Glycoprotein Hormones and Suggests that Cyclic Adenosine 3′,5′-Monophosphate Production and Growth Promotion are Potentially Dissociable Functions of Human Thyrotropin

Abstract

Amino acid residues 33-44 of the common α-subunit of the glycoprotein hormones have been implicated in heterodimerization as well as high affinity receptor binding of human (h) CG. In the present study, we compared the role of specific amino acids within this region for glycoprotein hormone heterodimer formation, using a transient transfection system to coexpress different mutant a-subunit constructs with the β-subunit of either hTSH, hCG, or hFSH. Our results identified a crucial role for αPro38 in the heterodimer expression of hTSH as well as hFSH, similar to what had been described for hCG. In contrast, αAla36, which had been critical for hCG, was not essential for hTSH heterodimer expres..