View source for 9bkj


==Cholecystokinin 1 receptor (CCK1R) Y140A mutant, Gq chimera (mGsqi) complex==
<StructureSection load='9bkj' size='340' side='right'caption='[[9bkj]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bkj]] 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=9BKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BKJ 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]] 2.59&#8491;</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=9bkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bkj OCA], [https://pdbe.org/9bkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bkj RCSB], [https://www.ebi.ac.uk/pdbsum/9bkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bkj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] 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.<ref>PMID:18611381</ref> 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bkj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Belousoff MJ]]
[[Category: Cary BP]]
[[Category: Christopoulos A]]
[[Category: Desai AJ]]
[[Category: Furness SGB]]
[[Category: Harikumar KG]]
[[Category: Miller LJ]]
[[Category: Mobbs JM]]
[[Category: Sexton PM]]
[[Category: Toufaily C]]
[[Category: Wootten D]]
[[Category: Zhao P]]