4ay9

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

spinqualitylabelsall models 4ay9, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ay9 is a 9 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: NAG, TYS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLHA_HUMAN Publication Abstract from PubMed FSH, a glycoprotein hormone, and the FSH receptor (FSHR), a G protein-coupled receptor, play central roles in human reproduction. We report the crystal structure of FSH in complex with the entire extracellular domain of FSHR (FSHR(ED)), including the enigmatic hinge region that is responsible for signal specificity. Surprisingly, the hinge region does not form a separate structural unit as widely anticipated but is part of the integral structure of FSHR(ED). In addition to the known hormone-binding site, FSHR(ED) provides interaction sites with the hormone: a sulfotyrosine (sTyr) site in the hinge region consistent with previous studies and a potential exosite resulting from putative receptor trimerization. Our structure, in comparison to others, suggests FSHR interacts with its ligand in two steps: ligand recruitment followed by sTyr recognition. FSH first binds to the high-affinity hormone-binding subdomain of FSHR and reshapes the ligand conformation to form a sTyr-binding pocket. FSHR then inserts its sTyr (i.e., sulfated Tyr335) into the FSH nascent pocket, eventually leading to receptor activation. Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor.,Jiang X, Liu H, Chen X, Chen PH, Fischer D, Sriraman V, Yu HN, Arkinstall S, He X Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12491-6. Epub 2012 Jul 16. PMID:22802634 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Follicle-stimulating hormone Human Follicle-Stimulating Hormone Complexed with its Receptor

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