Year of Publication

2005

Document Type

Dissertation

College

Arts and Sciences

Department

Biology

First Advisor

Tae H. Ji

Abstract

Follicle stimulating hormone (FSH) comprises an ?? subunit and a ?? subunit,whereas the FSH receptor consists of two halves with distinct functions, the N-terminalextracellular exodomain and C-terminal membrane associated endodomain. FSH initiallybinds to exodomain, and the resulting FSH/exodomain complex modulates the endodomainand generates signal. However, it has been difficult to determine which subunit of FSHcontacts the exodomain or endodomain, and in what orientation FSH interacts with them.To address these crucial issues, the receptor was Ala-scanned and the hormone subunitswere probed with photoaffinity labeling with receptor peptides corresponding to the Nterminalregion of the exodomain and exoloop 3 of the endodomain. The results show thatboth regions of the receptors are important for hormone binding and signal generation. Inaddition, the FSH ?? subunit is specifically labeled with the N-terminal peptide, whereas the?? subunit is labeled with the exoloop 3 peptide. These contrasting results show that the FSH?? subunit is close to the N-terminal region and the ?? subunit is projected toward exoloop 3in the endodomain. The results raise the fundamental question whether the ?? subunit,common among the glycoprotein hormones, plays a major role in generating the hormonesignal common to all glycoprotein hormones.

Share

COinS