8ha0: Difference between revisions
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==Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1== | |||
<StructureSection load='8ha0' size='340' side='right'caption='[[8ha0]], [[Resolution|resolution]] 2.62Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ha0]] 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=8HA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HA0 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]] 2.62Å</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=8ha0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ha0 OCA], [https://pdbe.org/8ha0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ha0 RCSB], [https://www.ebi.ac.uk/pdbsum/8ha0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ha0 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 A and 3.25 A, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders. | |||
Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.,Zhao LH, Yuan QN, Dai AT, He XH, Chen CW, Zhang C, Xu YW, Zhou Y, Wang MW, Yang DH, Xu HE Acta Pharmacol Sin. 2023 Jun;44(6):1227-1237. doi: 10.1038/s41401-022-01032-z. , Epub 2022 Dec 8. PMID:36482086<ref>PMID:36482086</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8ha0" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Yuan | ==See Also== | ||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Xu HE]] | |||
[[Category: Yuan Q]] | |||
[[Category: Zhao L]] | |||
Latest revision as of 12:40, 17 October 2024
Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1
Structural highlights
Publication Abstract from PubMedParathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 A and 3.25 A, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders. Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.,Zhao LH, Yuan QN, Dai AT, He XH, Chen CW, Zhang C, Xu YW, Zhou Y, Wang MW, Yang DH, Xu HE Acta Pharmacol Sin. 2023 Jun;44(6):1227-1237. doi: 10.1038/s41401-022-01032-z. , Epub 2022 Dec 8. PMID:36482086[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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