View source for 6nbi


==Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein==
<SX load='6nbi' size='340' side='right' viewer='molstar' caption='[[6nbi]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nbi]] 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=6NBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NBI 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]] 4&#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></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=6nbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbi OCA], [https://pdbe.org/6nbi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nbi RCSB], [https://www.ebi.ac.uk/pdbsum/6nbi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GNAI1_BOVIN GNAI1_BOVIN] Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (By similarity). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (By similarity). Required for cortical dynein-dynactin complex recruitment during metaphase (By similarity).[UniProtKB:P10824][UniProtKB:P63096][https://www.uniprot.org/uniprot/GNAS2_BOVIN GNAS2_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli.
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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 6nbi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
*[[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]]