8haf: Difference between revisions
New page: '''Unreleased structure''' The entry 8haf is ON HOLD Authors: Zhao, L., Xu, H.E., Yuan, Q. Description: PTHrP-PTH1R-Gs complex Category: Unreleased Structures Category: Xu, H.E... |
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==PTHrP-PTH1R-Gs complex== | |||
<StructureSection load='8haf' size='340' side='right'caption='[[8haf]], [[Resolution|resolution]] 3.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8haf]] 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=8HAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HAF 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=NH2:AMINO+GROUP'>NH2</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=8haf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8haf OCA], [https://pdbe.org/8haf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8haf RCSB], [https://www.ebi.ac.uk/pdbsum/8haf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8haf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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. | |||
<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. 2022 Dec 8. doi: 10.1038/s41401-022-01032-z. 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 8haf" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Yuan | <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 12:31, 21 December 2022
PTHrP-PTH1R-Gs complexPTHrP-PTH1R-Gs complex
Structural highlights
FunctionGBB1_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. 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. 2022 Dec 8. doi: 10.1038/s41401-022-01032-z. PMID:36482086[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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