| Institution: | 1. Department of Genetics, College of Science, Kazerun Branch, Islamic Azad University, Kāzerūn, Iran;2. Department of Pathology, Osmania General Hospital, Hyderabad, India;3. Division of Animal Health, Computational Lab, Daskdān Biotech Solutions Ltd, Srinagar, India;4. Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, India;5. Department of Bioinformatics, School of Life Sciences, Vels University, Chennai, India;6. Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada;7. Department of Biology, Payame Noor University, Iran;8. Department of Medical Biotechnology, School of Bioscience and Technology, VIT University, Vellore, India;9. Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST-Kashmir, Shuhama, Srinagar, Jammu and Kashmir, India |
| Abstract: | 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. |
