4mqw

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{{STRUCTURE_4mqw| PDB=4mqw | SCENE= }}
 
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===Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor (P31)===
 
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==Disease==
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==Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor (P31)==
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[[http://www.uniprot.org/uniprot/FSHR_HUMAN FSHR_HUMAN]] Defects in FSHR are a cause of ovarian dysgenesis type 1 (ODG1) [MIM:[http://omim.org/entry/233300 233300]]; also known as premature ovarian failure or gonadal dysgenesis XX type or XX gonadal dysgenesis (XXGD) or hereditary hypergonadotropic ovarian failure or hypergonadotropic ovarian dysgenesis with normal karyotype. ODG1 is an autosomal recessive disease characterized by primary amenorrhea, variable development of secondary sex characteristics, and high serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).<ref>PMID:7553856</ref> <ref>PMID:9851774</ref> <ref>PMID:9769327</ref> <ref>PMID:10551778</ref> <ref>PMID:11889179</ref> <ref>PMID:12571157</ref> <ref>PMID:12915623</ref> Defects in FSHR are a cause of ovarian hyperstimulation syndrome (OHSS) [MIM:[http://omim.org/entry/608115 608115]]. OHSS is a disorder which occurs either spontaneously or most often as an iatrogenic complication of ovarian stimulation treatments for in vitro fertilization. The clinical manifestations vary from abdominal distention and discomfort to potentially life-threatening, massive ovarian enlargement and capillary leak with fluid sequestration. Pathologic features of this syndrome include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis.<ref>PMID:12930927</ref> <ref>PMID:12930928</ref> <ref>PMID:15080154</ref> <ref>PMID:16278261</ref> <ref>PMID:17721928</ref> [[http://www.uniprot.org/uniprot/FSHB_HUMAN FSHB_HUMAN]] Defects in FSHB are a cause of isolated follicle-stimulating hormone deficiency (IFSHD) [MIM:[http://omim.org/entry/229070 229070]]. Selective follicle-stimulating hormone deficiency is an uncommon cause of infertility, producing amenorrhea and hypogonadism in women and oligo or azoospermia with normal testosterone levels in normally virilised men.<ref>PMID:8220432</ref> <ref>PMID:9271483</ref> <ref>PMID:9280841</ref>
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<StructureSection load='4mqw' size='340' side='right'caption='[[4mqw]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4mqw]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MQW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MQW FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JEF:O-(O-(2-AMINOPROPYL)-O-(2-METHOXYETHYL)POLYPROPYLENE+GLYCOL+500)'>JEF</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mqw OCA], [https://pdbe.org/4mqw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mqw RCSB], [https://www.ebi.ac.uk/pdbsum/4mqw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mqw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GLHA_HUMAN GLHA_HUMAN]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Follicle stimulating hormone receptor (FSHR), a G-protein coupled receptor (GPCR), is an important drug target in the development of novel therapeutics for reproductive indications. The FSHR extracellular domains are 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 N52alpha-deglycosylated FSH at a three-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 three-fold, and that the dissociated monomers would in turn enhance FSHR binding and signaling activities by three-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 (TSHR) autoantibodies. We conclude that FSHR exists as a functional trimer.
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==Function==
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Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer.,Jiang X, Fischer D, Chen X, McKenna SD, Liu H, Sriraman V, Yu HN, Goutopoulos A, Arkinstall S, He X J Biol Chem. 2014 Apr 2. PMID:24692546<ref>PMID:24692546</ref>
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[[http://www.uniprot.org/uniprot/FSHR_HUMAN FSHR_HUMAN]] Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. [[http://www.uniprot.org/uniprot/FSHB_HUMAN FSHB_HUMAN]] Stimulates development of follicle and spermatogenesis in the reproductive organs.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4mqw]] is a 9 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MQW OCA].
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</div>
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<div class="pdbe-citations 4mqw" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<references group="xtra"/><references/>
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*[[Follicle-stimulating hormone|Follicle-stimulating hormone]]
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[[Category: Chen, X.]]
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== References ==
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[[Category: He, X.]]
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<references/>
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[[Category: Jiang, X.]]
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__TOC__
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[[Category: Liu, H.]]
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</StructureSection>
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[[Category: Cystine-knot]]
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[[Category: Homo sapiens]]
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[[Category: Glycoprotein hormone]]
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[[Category: Large Structures]]
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[[Category: Gpcr]]
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[[Category: Chen X]]
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[[Category: Leucine-rich repeat]]
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[[Category: He X]]
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[[Category: Signaling protein]]
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[[Category: Jiang X]]
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[[Category: Sulfation]]
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[[Category: Liu H]]

Current revision

Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor (P31)

PDB ID 4mqw

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