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D224V and S128Y mutation in FSHR ED influence thumb movement differentially: An intricate insight gained by short‐term molecular dynamics simulation
Gharemirshamlu F.R, Afsar M, Mokhdomi T.A, Amin A, Bukhari S, , Kumar C.V, Bamdad K, , Qadri R.AShow More
Published in Wiley
Volume: 120
Issue: 5
Pages: 7701 - 7710
Follicle-stimulating hormone-follicle-stimulating hormone receptor (FSH-FSHR) interaction is one of the most thoroughly studied signaling pathways primarily because of being implicated in sexual reproduction in mammals by way of maintaining gonadal function and sexual fertility. Despite material advances in understanding the role of point mutations, their mechanistic basis in FSH-FSHR signaling is still confined to mystically altered behavior of sTYS335 (sulfated tyrosine) yet lacking a substantial theory. To understand the structural basis of receptor modulation, we choose two behaviorally contradicting mutations, namely S128Y (activating) and D224Y (inactivating), found in FSH receptor responsible for ovarian hyperstimulation syndrome and ovarian dysgenesis, respectively. Using short-term molecular dynamics simulations, the atomic scale investigations reveal that the binding pattern of sTYS with FSH and movement of the thumb region of FSHR show distinct contrasting patterns in the two mutants, which supposedly could be a critical factor for differential FSHR behavior in activating and inactivating mutations. © 2018 Wiley Periodicals, Inc.
About the journal
JournalData powered by TypesetJournal of Cellular Biochemistry
PublisherData powered by TypesetWiley
Open Access0