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6nbi

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Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein

6nbi, resolution 4.00Å

Structural highlights

6nbi is a 6 chain structure with sequence from Bovin, Buffalo rat, Human and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	PTH1R, PTHR, PTHR1 (HUMAN), Gnb1 (Buffalo rat), GNG2 (BOVIN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[GBB1_RAT] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [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.^[1] ^[2] [GBG2_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Johnston CA, Kimple AJ, Giguere PM, Siderovski DP. Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2. Structure. 2008 Jul;16(7):1086-94. PMID:18611381 doi:http://dx.doi.org/10.1016/j.str.2008.04.010
↑ Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE. Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation. J Biol Chem. 2010 Apr 16;285(16):12435-44. Epub 2010 Feb 19. PMID:20172855 doi:10.1074/jbc.M109.093138
↑ 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. Structure and dynamics of the active human parathyroid hormone receptor-1. Science. 2019 Apr 12;364(6436):148-153. doi: 10.1126/science.aav7942. PMID:30975883 doi:http://dx.doi.org/10.1126/science.aav7942

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6nbi"

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Bovin Bovin], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat], [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NBI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6nbi]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat], [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. 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 [http://proteopedia.org/fgij/fg.htm?mol=6NBI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTH1R, PTHR, PTHR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Gnb1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbi OCA], [http://pdbe.org/6nbi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nbi RCSB], [http://www.ebi.ac.uk/pdbsum/6nbi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbi ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6nbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbi OCA], [http://pdbe.org/6nbi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nbi RCSB], [http://www.ebi.ac.uk/pdbsum/6nbi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbi ProSAT]</span></td></tr>
 </table>
 == Disease ==

6nbi

From Proteopedia

Current revision

Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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