7xow
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7xow]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7XOW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XOW FirstGlance]. <br> | <table><tr><td colspan='2'>[[7xow]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7XOW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XOW FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></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]] 3.1Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7xow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xow OCA], [https://pdbe.org/7xow PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xow RCSB], [https://www.ebi.ac.uk/pdbsum/7xow PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xow 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=7xow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xow OCA], [https://pdbe.org/7xow PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xow RCSB], [https://www.ebi.ac.uk/pdbsum/7xow PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xow ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/GASR_HUMAN GASR_HUMAN] Receptor for gastrin and cholecystokinin. The CKK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.<ref>PMID:8349705</ref> <ref>PMID:8185170</ref> <ref>PMID:7848914</ref> <ref>PMID:10913157</ref> <ref>PMID:11495676</ref> <ref>PMID:8221657</ref> Isoform 2 is constitutively activated and may regulate cancer cell proliferation via a gastrin-independent mechanism.<ref>PMID:8349705</ref> <ref>PMID:8185170</ref> <ref>PMID:7848914</ref> <ref>PMID:10913157</ref> <ref>PMID:11495676</ref> <ref>PMID:8221657</ref> | |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain-gut axis, mediating digestion, emotion, and memory regulation. CCK receptors exhibit distinct preferences for ligands in different posttranslational modification (PTM) states. CCK1R couples to G(s) and G(q), whereas CCK2R primarily couples to G(q). Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R-G(s) signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R-G(q) complexes stabilized by either sulfated CCK-8 or a CCK2R-selective ligand gastrin-17. Our structures reveal a location-conserved yet charge-distinct pocket discriminating the effects of ligand PTM states on receptor subtype preference, the unique pocket topology underlying selectivity of SR146131 and gastrin-17, the conformational changes in receptor activation, and key residues contributing to G protein subtype specificity, providing multiple structural templates for drug design targeting the brain-gut axis. | ||
| + | |||
| + | Structural insights into human brain-gut peptide cholecystokinin receptors.,Ding Y, Zhang H, Liao YY, Chen LN, Ji SY, Qin J, Mao C, Shen DD, Lin L, Wang H, Zhang Y, Li XM Cell Discov. 2022 Jun 7;8(1):55. doi: 10.1038/s41421-022-00420-3. PMID:35672283<ref>PMID:35672283</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7xow" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Transducin 3D structures|Transducin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structural insights into human brain gut peptide cholecystokinin receptors
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Categories: Homo sapiens | Large Structures | Mus musculus | Chen L | Ding Y | Ji S | Liao Y | Zhang H
