9bkk
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[9bkk]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BKK FirstGlance]. <br> | <table><tr><td colspan='2'>[[9bkk]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BKK 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]] 2.51Å</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]] 2.51Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</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=9bkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bkk OCA], [https://pdbe.org/9bkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bkk RCSB], [https://www.ebi.ac.uk/pdbsum/9bkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bkk 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=9bkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bkk OCA], [https://pdbe.org/9bkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bkk RCSB], [https://www.ebi.ac.uk/pdbsum/9bkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bkk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Disease == | ||
| - | [https://www.uniprot.org/uniprot/GNAS1_HUMAN GNAS1_HUMAN] The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed. The disease is caused by variants affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/CCKN_HUMAN CCKN_HUMAN] This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release from the pancreas, binding to CCK-B receptors stimulates gastric acid secretion.[UniProtKB:Q9TS44] |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Development of optimal therapeutics for disease states that can be associated with increased membrane cholesterol requires better molecular understanding of lipid modulation of the drug target. Type 1 cholecystokinin receptor (CCK1R) agonist actions are affected by increased membrane cholesterol, enhancing ligand binding and reducing calcium signaling, while agonist actions of the closely related CCK2R are not. In this work, we identified a set of chimeric human CCK1R/CCK2R mutations that exchange the cholesterol sensitivity of these 2 receptors, providing powerful tools when expressed in CHO and HEK-293 model cell lines to explore mechanisms. Static, low energy, high-resolution structures of the mutant CCK1R constructs, stabilized in complex with G protein, were not substantially different, suggesting that alterations to receptor dynamics were key to altered function. We reveal that cholesterol-dependent dynamic changes in the conformation of the helical bundle of CCK receptors affects both ligand binding at the extracellular surface and G protein coupling at the cytosolic surface, as well as their interrelationships involved in stimulus-response coupling. This provides an ideal setting for potential allosteric modulators to correct the negative impact of membrane cholesterol on CCK1R. | ||
| + | |||
| + | Cholesterol-dependent dynamic changes in the conformation of the type 1 cholecystokinin receptor affect ligand binding and G protein coupling.,Harikumar KG, Zhao P, Cary BP, Xu X, Desai AJ, Dong M, Mobbs JI, Toufaily C, Furness SGB, Christopoulos A, Belousoff MJ, Wootten D, Sexton PM, Miller LJ PLoS Biol. 2024 Jul 31;22(7):e3002673. doi: 10.1371/journal.pbio.3002673. , eCollection 2024 Jul. PMID:39083706<ref>PMID:39083706</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 9bkk" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Cholecystokinin 1 receptor (CCK1R) sterol 7M mutant, Gq chimera (mGsqi) complex
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Categories: Homo sapiens | Large Structures | Belousoff MJ | Cary BP | Christopoulos A | Desai AJ | Furness SGB | Harikumar KG | Miller LJ | Mobbs JI | Sexton PM | Toufaily C | Wootten D | Xu X | Zhao P
