8ia7

From Proteopedia

(Difference between revisions)

Revision as of 07:58, 6 December 2023

Structural insights into human brain gut peptide cholecystokinin receptors

Structural highlights

8ia7 is a 6 chain structure with sequence from Homo sapiens and Mus musculus. This structure supersedes the now removed PDB entry 7xox. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.1Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] Isoform 2 is constitutively activated and may regulate cancer cell proliferation via a gastrin-independent mechanism.^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

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^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, Nakata H, Chiba T, Chihara K. Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin. J Biol Chem. 1993 Aug 25;268(24):18300-5. PMID:8349705
↑ Herget T, Sethi T, Wu SV, Walsh JH, Rozengurt E. Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors. Ann N Y Acad Sci. 1994 Mar 23;713:283-97. PMID:8185170
↑ Ito M, Iwata N, Taniguchi T, Murayama T, Chihara K, Matsui T. Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene. Cell Growth Differ. 1994 Oct;5(10):1127-35. PMID:7848914
↑ Hellmich MR, Rui XL, Hellmich HL, Fleming RY, Evers BM, Townsend CM Jr. Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth. J Biol Chem. 2000 Oct 13;275(41):32122-8. PMID:10913157 doi:http://dx.doi.org/10.1074/jbc.M005754200
↑ Schmitz F, Schrader H, Otte J, Schmitz H, Stuber E, Herzig K, Schmidt WE. Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells. Regul Pept. 2001 Sep 15;101(1-3):25-33. PMID:11495676
↑ Sethi T, Herget T, Wu SV, Walsh JH, Rozengurt E. CCKA and CCKB receptors are expressed in small cell lung cancer lines and mediate Ca2+ mobilization and clonal growth. Cancer Res. 1993 Nov 1;53(21):5208-13. PMID:8221657
↑ Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, Nakata H, Chiba T, Chihara K. Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin. J Biol Chem. 1993 Aug 25;268(24):18300-5. PMID:8349705
↑ Herget T, Sethi T, Wu SV, Walsh JH, Rozengurt E. Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors. Ann N Y Acad Sci. 1994 Mar 23;713:283-97. PMID:8185170
↑ Ito M, Iwata N, Taniguchi T, Murayama T, Chihara K, Matsui T. Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene. Cell Growth Differ. 1994 Oct;5(10):1127-35. PMID:7848914
↑ Hellmich MR, Rui XL, Hellmich HL, Fleming RY, Evers BM, Townsend CM Jr. Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth. J Biol Chem. 2000 Oct 13;275(41):32122-8. PMID:10913157 doi:http://dx.doi.org/10.1074/jbc.M005754200
↑ Schmitz F, Schrader H, Otte J, Schmitz H, Stuber E, Herzig K, Schmidt WE. Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells. Regul Pept. 2001 Sep 15;101(1-3):25-33. PMID:11495676
↑ Sethi T, Herget T, Wu SV, Walsh JH, Rozengurt E. CCKA and CCKB receptors are expressed in small cell lung cancer lines and mediate Ca2+ mobilization and clonal growth. Cancer Res. 1993 Nov 1;53(21):5208-13. PMID:8221657
↑ Ding Y, Zhang H, Liao YY, Chen LN, Ji SY, Qin J, Mao C, Shen DD, Lin L, Wang H, Zhang Y, Li XM. Structural insights into human brain-gut peptide cholecystokinin receptors. Cell Discov. 2022 Jun 7;8(1):55. PMID:35672283 doi:10.1038/s41421-022-00420-3

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8ia7"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8ia7 is ON HOLD
+==Structural insights into human brain gut peptide cholecystokinin receptors==
+<StructureSection load='8ia7' size='340' side='right'caption='[[8ia7]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ia7]] 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]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=7xox 7xox]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IA7 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]] 3.1&#8491;</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=8ia7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ia7 OCA], [https://pdbe.org/8ia7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ia7 RCSB], [https://www.ebi.ac.uk/pdbsum/8ia7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ia7 ProSAT]</span></td></tr>
+</table>
+== 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.
-Authors: Ding, Y., Zhang, H., Liao, Y., Chen, L., Ji, S.
+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>
-Description: Structural insights into human brain gut peptide cholecystokinin receptors
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Zhang, H]]
+<div class="pdbe-citations 8ia7" style="background-color:#fffaf0;"></div>
-[[Category: Ji, S]]
+== References ==
-[[Category: Ding, Y]]
+<references/>
-[[Category: Liao, Y]]
+__TOC__
-[[Category: Chen, L]]
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Chen L]]
+[[Category: Ding Y]]
+[[Category: Ji S]]
+[[Category: Liao Y]]
+[[Category: Zhang H]]

8ia7

From Proteopedia

Revision as of 07:58, 6 December 2023

Structural insights into human brain gut peptide cholecystokinin receptors

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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