Expression of Biologically Active Fusion Genes Encoding the Common Subunit and the Follicle-stimulating Hormone Subunit

• Published in: The Journal of biological chemistry Vol. 271; no. 18; p. 10445
• Main Authors: Tadashi Sugahara, Asomi Sato, Masataka Kudo, David Ben-Menahem, Mary R. Pixley, Aaron J. W. Hsueh, Irving Boime
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 03.05.1996
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.18.10445

The gonadotropin/thyrotropin hormone family is characterized by a heterodimeric structure composed of a common α subunit noncovalently linked to a hormone-specific β subunit. The conformation of the heterodimer is essential for controlling secretion, hormone-specific post-translational modifications, and signal transduction. Structure-function studies of follicle-stimulating hormone (FSH) and the other glycoprotein hormones are often hampered by mutagenesis-induced defects in subunit combination. Thus, the ability to overcome the limitation of subunit assembly would expand the range of structure-activity relationships that can be performed on these hormones. Here we converted the FSH heterodimer to a single chain by genetically fusing the carboxyl end of the FSH β subunit to the amino end of the α subunit in the presence or absence of a linker sequence. In the absence of the CTP linker, the secretion rate was decreased over 3-fold. Unexpectedly, however, receptor binding/signal transduction was unaffected by the absence of the linker. These data show that the single-chain FSH was secreted efficiently and is biologically active and that the conformation determinants required for secretion and biologic activity are not the same.