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Your search keyword '"McKenna, Sean A."' showing total 9 results
Start Over Author "McKenna, Sean A." Journal journal of biological chemistry
9 results on '"McKenna, Sean A."'

9. Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer.

Author

Xuliang Jiang, Fischer, David, Xiaoyan Chen, McKenna, Sean D., Heli Liu, Sriraman, Venkataraman, Yu, Henry N., Goutopoulos, Andreas, Arkinstall, Steve, and Xiaolin He

Subjects
*FOLLICLE-stimulating hormone receptor, *MONOMERS, *CRYSTALLOGRAPHY, *MUTAGENESIS, *AUTOANTIBODIES
Abstract

Follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor, is an important drug target in the development of novel therapeutics for reproductive indications. The FSHR extracellular domains were observed in the crystal structure as a trimer, which enabled us to propose a novel model for the receptor activation mechanism. The model predicts that FSHR binds Asnα52-deglycosylated FSH at a 3-fold higher capacity than fully glycosylated FSH. It also predicts that, upon dissociation of the FSHR trimer into monomers, the binding of glycosylated FSH, but not deglycosylated FSH, would increase 3-fold, and that the dissociated monomers would in turn enhance FSHR binding and signaling activities by 3-fold. This study presents evidence confirming these predictions and provides crystallographic and mutagenesis data supporting the proposed model. The model also provides a mechanistic explanation to the agonist and antagonist activities of thyroid-stimulating hormone receptor autoantibodies. We conclude that FSHR exists as a functional trimer. [ABSTRACT FROM AUTHOR]

Published
2014
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