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dc.contributor.authorMeher, Biswa Ranjan
dc.contributor.authorDixit, Anshuman
dc.contributor.authorBousfield, George R.
dc.contributor.authorLushington, Gerald H.
dc.date.accessioned2015-10-28T20:36:50Z
dc.date.available2015-10-28T20:36:50Z
dc.date.issued2015-09-24
dc.identifier.citationMeher BR, Dixit A, Bousfield GR, Lushington GH (2015) Glycosylation Effects on FSH-FSHR Interaction Dynamics: A Case Study of Different FSH Glycoforms by Molecular Dynamics Simulations. PLoS ONE 10(9): e0137897en_US
dc.identifier.issn1932-6203
dc.identifier.otherWOS:000361798100014
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0137897
dc.identifier.urihttp://hdl.handle.net/10057/11563
dc.descriptionThis is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedicationen_US
dc.description.abstractThe gonadotropin known as follicle-stimulating hormone (FSH) plays a key role in regulating reproductive processes. Physiologically active FSH is a glycoprotein that can accommodate glycans on up to four asparagine residues, including two sites in the FSH alpha subunit that are critical for biochemical function, plus two sites in the beta subunit, whose differential glycosylation states appear to correspond to physiologically distinct functions. Some degree of FSH beta hypo-glycosylation seems to confer advantages toward reproductive fertility of childbearing females. In order to identify possible mechanistic underpinnings for this physiological difference we have pursued computationally intensive molecular dynamics simulations on complexes between the high affinity site of the gonadal FSH receptor (FSHR) and several FSH glycoforms including fully-glycosylated (FSH24), hypo-glycosylated (e.g., FSH15), and completely deglycosylated FSH (dgFSH). These simulations suggest that deviations in FSH/FSHR binding profile as a function of glycosylation state are modest when FSH is adorned with only small glycans, such as single N-acetylglucosamine residues. However, substantial qualitative differences emerge between FSH15 and FSH24 when FSH is decorated with a much larger, tetra-antennary glycan. Specifically, the FSHR complex with hypo-glycosylated FSH15 is observed to undergo a significant conformational shift after 5-10 ns of simulation, indicating that FSH15 has greater conformational flexibility than FSH24 which may explain the more favorable FSH15 kinetic profile. FSH15 also exhibits a stronger binding free energy, due in large part to formation of closer and more persistent salt-bridges with FSHR.en_US
dc.description.sponsorshipThis research was supported by National Institute of Health Grant P01 AG-029531 to GRB. LiS Consulting provided support in the form of a salary for GHL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the 'author contributions' section.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofseriesPLoS ONE;v.10:no.9
dc.rightsOpen Access
dc.subjectFollicle-stimulating-hormoneen_US
dc.subjectIn-vitroen_US
dc.subjectReceptoren_US
dc.subjectRolesen_US
dc.subjectWateren_US
dc.subjectResiduesen_US
dc.subjectComplexen_US
dc.subjectBbindingen_US
dc.subjectModelsen_US
dc.subjectSystemen_US
dc.titleGlycosylation effects on FSH-FSHR interaction dynamics: a case study of different FSH glycoforms by molecular dynamics simulationsen_US
dc.typeArticleen_US
dc.rights.holderThe copyright in the material contained on the PLOS Sites belongs to PLOS or its licensors.en_US


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