Expression of biologically active fusion genes encoding the common α subunit and the follicle-stimulating hormone β subunit: Role of a linker sequence

Tadashi Sugahara, Asomi Sato, Masataka Rudolf, David Ben-Menahem, Mary R. Pixley, Aaron J.W. Hsueh, Irving Boime

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)10445-10448
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number18
DOIs
StatePublished - May 20 1996

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