8jgb - Revision history

OCA at 10:24, 10 January 2024

2024-01-10T10:24:55Z

← Older revision		Revision as of 10:24, 10 January 2024
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8jgb is ~~ON HOLD until Paper~~ Publication		==CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist CNF-Tx2==
			<StructureSection load='8jgb' size='340' side='right'caption='[[8jgb]], [[Resolution\|resolution]] 2.84Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8jgb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_textile Conus textile] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JGB 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]] 2.84Å</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=8jgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jgb OCA], [https://pdbe.org/8jgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jgb RCSB], [https://www.ebi.ac.uk/pdbsum/8jgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jgb ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/CRFA2_CONTE CRFA2_CONTE] This peptide activates human sensory neuron-specific G-protein coupled receptors MRGPRX1, but not mouse receptors (EC(50)=0.54 uM) (PubMed:30243794). Compared with the agonist chloroquine (anti-malaria drug), it is 600-fold more potent (PubMed:30243794). In vivo, induces itch sensation, since intradermal cheek injection into humanized transgenic mouse (mouse MRGPRX1 replaced by human MRGPRX1) induces scratching (PubMed:30243794). In vivo, treatment of zebrafish larvae with high doses (10 uM) induces hypoactivity at the beginning of the experiment during the dark phase and hyperactivity in the strobe phase after one hour, even after the removal of the toxin from the solution (PubMed:33764053).<ref>PMID:30243794</ref> <ref>PMID:33764053</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal "RF/RY" motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the G(6.48)XP(6.50)F(6.51)G(6.52)X((2))F/W(6.55) motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling.

	~~Authors: Sun~~, ~~J.P.~~, Xu, ~~H.E.~~, ~~Yang~~, F., Liu, Z.M., ~~Guo~~, L~~.L.~~, ~~Zhang~~, Y~~.M.~~, ~~Fang~~, G.X., ~~Tie~~, L., ~~Zhuang~~, Y.M.~~, Xue, C~~.Y.		Ligand recognition and G protein coupling of the human itch receptor MRGPRX1.,Guo L, Zhang Y, Fang G, Tie L, Zhuang Y, Xue C, Liu Q, Zhang M, Zhu K, You C, Xu P, Yuan Q, Zhang C, Liu L, Rong N, Peng S, Liu Y, Wang C, Luo X, Lv Z, Kang D, Yu X, Zhang C, Jiang Y, Dong X, Zhou J, Liu Z, Yang F, Eric Xu H, Sun JP Nat Commun. 2023 Aug 17;14(1):5004. doi: 10.1038/s41467-023-40705-z. PMID:37591889<ref>PMID:37591889</ref>

	~~Description: CryoEM structure~~ of Gi-~~coupled MRGPRX1 with peptide agonist CNF~~-~~Tx2~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased Structures~~]]		</div>
	[[Category: ~~Xu, H.E~~]]		<div class="pdbe-citations 8jgb" style="background-color:#fffaf0;"></div>
	[[Category: ~~Zhang, Y.M~~]]		== References ==
	[[Category: ~~Tie, L~~]]		<references/>
	[[Category: ~~Sun, J.P~~]]		__TOC__
	[[Category: ~~Xue, C.Y~~]]		</StructureSection>
	[[Category: ~~Fang, G.X~~]]		[[Category: Conus textile]]
	[[Category: ~~Guo, L.~~L]]		[[Category: Homo sapiens]]
	[[Category: ~~Liu, Z.M~~]]		[[Category: Large Structures]]
	[[Category: Yang, F]]		[[Category: Fang GX]]
	[[Category: Zhuang~~, Y.M~~]]		[[Category: Guo LL]]
			[[Category: Liu ZM]]
			[[Category: Sun JP]]
			[[Category: Tie L]]
			[[Category: Xu HE]]
			[[Category: Xue CY]]
			[[Category: Yang F]]
			[[Category: Zhang YM]]
			[[Category: Zhuang YM]]

OCA at 04:36, 19 July 2023

2023-07-19T04:36:36Z

← Older revision		Revision as of 04:36, 19 July 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8jgb is ON HOLD		The entry 8jgb is ON HOLD until Paper Publication

	Authors: Sun, J.P., Xu, H.E., Yang, F., Liu, Z.M., Guo, L.L., Zhang, Y.M., Fang, G.X., Tie, L., Zhuang, Y.M., Xue, C.Y.		Authors: Sun, J.P., Xu, H.E., Yang, F., Liu, Z.M., Guo, L.L., Zhang, Y.M., Fang, G.X., Tie, L., Zhuang, Y.M., Xue, C.Y.
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	[[Category: Zhang, Y.M]]		[[Category: Zhang, Y.M]]
	[[Category: Tie, L]]		[[Category: Tie, L]]
	~~[[Category: Liu, Z.M]]~~
	[[Category: Sun, J.P]]		[[Category: Sun, J.P]]
	[[Category: Xue, C.Y]]		[[Category: Xue, C.Y]]
	~~[[Category: Yang, F]]~~
	[[Category: Fang, G.X]]		[[Category: Fang, G.X]]
	[[Category: Guo, L.L]]		[[Category: Guo, L.L]]
			[[Category: Liu, Z.M]]
			[[Category: Yang, F]]
	[[Category: Zhuang, Y.M]]		[[Category: Zhuang, Y.M]]

OCA at 03:55, 5 July 2023

2023-07-05T03:55:08Z

← Older revision		Revision as of 03:55, 5 July 2023
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	The entry 8jgb is ON HOLD		The entry 8jgb is ON HOLD

	Authors: Sun, J.P., Xu, H.E., Yang, F., Guo, L.L., Fang, G.X., Zhuang, Y.M.		Authors: Sun, J.P., Xu, H.E., Yang, F., Liu, Z.M., Guo, L.L., Zhang, Y.M., Fang, G.X., Tie, L., Zhuang, Y.M., Xue, C.Y.

	Description: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist CNF-Tx2		Description: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist CNF-Tx2
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Xu, H.E]]		[[Category: Xu, H.E]]
			[[Category: Zhang, Y.M]]
			[[Category: Tie, L]]
			[[Category: Liu, Z.M]]
	[[Category: Sun, J.P]]		[[Category: Sun, J.P]]
			[[Category: Xue, C.Y]]
	[[Category: Yang, F]]		[[Category: Yang, F]]
	[[Category: Fang, G.X]]		[[Category: Fang, G.X]]
	[[Category: Guo, L.L]]		[[Category: Guo, L.L]]
	[[Category: Zhuang, Y.M]]		[[Category: Zhuang, Y.M]]

OCA at 04:13, 7 June 2023

2023-06-07T04:13:45Z

← Older revision		Revision as of 04:13, 7 June 2023
Line 3:		Line 3:
	The entry 8jgb is ON HOLD		The entry 8jgb is ON HOLD

	Authors: Sun, J.P., Xu, H.~~Eric~~., Yang, F., Guo, L.L., Fang, G.X., ~~Zhunag~~, Y.M.		Authors: Sun, J.P., Xu, H.E., Yang, F., Guo, L.L., Fang, G.X., Zhuang, Y.M.

	Description: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist CNF-Tx2		Description: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist CNF-Tx2
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Xu, H.~~Eric~~]]		[[Category: Xu, H.E]]
	[[Category: Sun, J.P]]		[[Category: Sun, J.P]]
	[[Category: Yang, F]]		[[Category: Yang, F]]
	[[Category: Fang, G.X]]		[[Category: Fang, G.X]]
	[[Category: Guo, L.L]]		[[Category: Guo, L.L]]
	[[Category: ~~Zhunag~~, Y.M]]		[[Category: Zhuang, Y.M]]

OCA: Protected "8jgb" [edit=sysop:move=sysop]

2023-05-31T04:00:13Z

Protected "8jgb" [edit=sysop:move=sysop]

← Older revision	Revision as of 04:00, 31 May 2023
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8jgb is ON HOLD Authors: Sun, J.P., Xu, H.Eric., Yang, F., Guo, L.L., Fang, G.X., Zhunag, Y.M. Description: CryoEM structure of Gi-coupled MRGPRX1 ...

2023-05-31T04:00:10Z

New page: '''Unreleased structure''' The entry 8jgb is ON HOLD Authors: Sun, J.P., Xu, H.Eric., Yang, F., Guo, L.L., Fang, G.X., Zhunag, Y.M. Description: CryoEM structure of Gi-coupled MRGPRX1 ...

New page

'''Unreleased structure'''

The entry 8jgb is ON HOLD

Authors: Sun, J.P., Xu, H.Eric., Yang, F., Guo, L.L., Fang, G.X., Zhunag, Y.M.

Description: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist CNF-Tx2
[[Category: Unreleased Structures]]
[[Category: Xu, H.Eric]]
[[Category: Sun, J.P]]
[[Category: Yang, F]]
[[Category: Fang, G.X]]
[[Category: Guo, L.L]]
[[Category: Zhunag, Y.M]]