View source for 6nbf


==Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein==
<SX load='6nbf' size='340' side='right' viewer='molstar' caption='[[6nbf]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nbf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NBF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbf OCA], [https://pdbe.org/6nbf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nbf RCSB], [https://www.ebi.ac.uk/pdbsum/6nbf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PTH1R_HUMAN PTH1R_HUMAN] Blomstrand lethal chondrodysplasia;Dental ankylosis;Eiken syndrome;Metaphyseal chondrodysplasia, Jansen type;Enchondromatosis. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease may be caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/PTH1R_HUMAN PTH1R_HUMAN] This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system.<ref>PMID:18611381</ref> <ref>PMID:20172855</ref> 
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== Publication Abstract from PubMed ==
The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo-electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation.

Structure and dynamics of the active human parathyroid hormone receptor-1.,Zhao LH, Ma S, Sutkeviciute I, Shen DD, Zhou XE, de Waal PW, Li CY, Kang Y, Clark LJ, Jean-Alphonse FG, White AD, Yang D, Dai A, Cai X, Chen J, Li C, Jiang Y, Watanabe T, Gardella TJ, Melcher K, Wang MW, Vilardaga JP, Xu HE, Zhang Y Science. 2019 Apr 12;364(6436):148-153. doi: 10.1126/science.aav7942. PMID:30975883<ref>PMID:30975883</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6nbf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Synthetic construct]]
[[Category: Clark LJ]]
[[Category: Gardella TJ]]
[[Category: Jean-Alphonse FG]]
[[Category: Jiang Y]]
[[Category: Kang Y]]
[[Category: Li C-Y]]
[[Category: Ma S]]
[[Category: Melcher K]]
[[Category: Shen D-D]]
[[Category: Sutkeviciute I]]
[[Category: Vilardaga J-P]]
[[Category: Wang M-W]]
[[Category: Watanabe T]]
[[Category: White AD]]
[[Category: Xiao K]]
[[Category: Xu HE]]
[[Category: Yang D]]
[[Category: Zhang Y]]
[[Category: Zhao L-H]]
[[Category: Zhou XE]]
[[Category: De Waal PP]]