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| | <SX load='6nbf' size='340' side='right' viewer='molstar' caption='[[6nbf]], [[Resolution|resolution]] 3.00Å' scene=''> | | <SX load='6nbf' size='340' side='right' viewer='molstar' caption='[[6nbf]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nbf]] 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=6NBF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NBF FirstGlance]. <br> | + | <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='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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3Å</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='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'>[http://proteopedia.org/fgij/fg.htm?mol=6nbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbf OCA], [http://pdbe.org/6nbf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nbf RCSB], [http://www.ebi.ac.uk/pdbsum/6nbf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbf ProSAT]</span></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> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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. | + | [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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GBB1_RAT 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. [[http://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> [[http://www.uniprot.org/uniprot/GBG2_BOVIN 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. | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Clark, L J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Gardella, T J]] | + | [[Category: Clark LJ]] |
| - | [[Category: Jean-Alphonse, F G]] | + | [[Category: Gardella TJ]] |
| - | [[Category: Jiang, Y]] | + | [[Category: Jean-Alphonse FG]] |
| - | [[Category: Kang, Y]] | + | [[Category: Jiang Y]] |
| - | [[Category: Li, C Y]] | + | [[Category: Kang Y]] |
| - | [[Category: Ma, S]] | + | [[Category: Li C-Y]] |
| - | [[Category: Melcher, K]] | + | [[Category: Ma S]] |
| - | [[Category: Shen, D D]] | + | [[Category: Melcher K]] |
| - | [[Category: Sutkeviciute, I]] | + | [[Category: Shen D-D]] |
| - | [[Category: Vilardaga, J P]] | + | [[Category: Sutkeviciute I]] |
| - | [[Category: Waal, P P.de]]
| + | [[Category: Vilardaga J-P]] |
| - | [[Category: Wang, M W]] | + | [[Category: Wang M-W]] |
| - | [[Category: Watanabe, T]] | + | [[Category: Watanabe T]] |
| - | [[Category: White, A D]] | + | [[Category: White AD]] |
| - | [[Category: Xiao, K]] | + | [[Category: Xiao K]] |
| - | [[Category: Xu, H E]] | + | [[Category: Xu HE]] |
| - | [[Category: Yang, D]] | + | [[Category: Yang D]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Zhao, L H]] | + | [[Category: Zhao L-H]] |
| - | [[Category: Zhou, X E]] | + | [[Category: Zhou XE]] |
| - | [[Category: Class b gpcr]] | + | [[Category: De Waal PP]] |
| - | [[Category: Gpcr]]
| + | |
| - | [[Category: Gpcr-g protein complex]]
| + | |
| - | [[Category: Parathyroid hormone receptor]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
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
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]
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.
See Also
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
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