7ra3: Difference between revisions
New page: '''Unreleased structure''' The entry 7ra3 is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==cryo-EM of human Gastric inhibitory polypeptide receptor GIPR bound to GIP== | ||
<StructureSection load='7ra3' size='340' side='right'caption='[[7ra3]], [[Resolution|resolution]] 3.24Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7ra3]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RA3 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]] 3.24Å</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=7ra3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ra3 OCA], [https://pdbe.org/7ra3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ra3 RCSB], [https://www.ebi.ac.uk/pdbsum/7ra3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ra3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GIPR_HUMAN GIPR_HUMAN] This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist. | |||
Structural determinants of dual incretin receptor agonism by tirzepatide.,Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2116506119. doi: , 10.1073/pnas.2116506119. Epub 2022 Mar 25. PMID:35333651<ref>PMID:35333651</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7ra3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Feng D]] | |||
[[Category: Kobilka BK]] | |||
[[Category: Kobilka TS]] | |||
[[Category: Sloop KW]] | |||
[[Category: Sun B]] | |||
Latest revision as of 14:37, 30 October 2024
cryo-EM of human Gastric inhibitory polypeptide receptor GIPR bound to GIPcryo-EM of human Gastric inhibitory polypeptide receptor GIPR bound to GIP
Structural highlights
FunctionGIPR_HUMAN This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMedSignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist. Structural determinants of dual incretin receptor agonism by tirzepatide.,Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2116506119. doi: , 10.1073/pnas.2116506119. Epub 2022 Mar 25. PMID:35333651[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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