7try - Revision history

OCA at 08:58, 4 June 2025

2025-06-04T08:58:14Z

← Older revision		Revision as of 08:58, 4 June 2025
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	The ability to couple with multiple G protein subtypes, such as G(s), G(i/o), or G(q/11), by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G(s) protein, have been determined. However, no structure of class B GPCRs with G(q/11) has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G(11) and G(o). We compare these structures with the structure of CRF2R in complex with G(s) to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.		The ability to couple with multiple G protein subtypes, such as G(s), G(i/o), or G(q/11), by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G(s) protein, have been determined. However, no structure of class B GPCRs with G(q/11) has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G(11) and G(o). We compare these structures with the structure of CRF2R in complex with G(s) to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.

	~~Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.~~,~~Zhao LH, Lin J, Ji SY, Zhou XE, Mao C, Shen DD, He X, Xiao P, Sun J, Melcher K, Zhang Y, Yu X, Xu HE Nat Commun. 2022 Nov 5;13(1):6670. doi: 10.1038/s41467-022-33851-3.~~ PMID:36335102<ref>PMID:36335102</ref>		, PMID:36335102<ref>PMID:36335102</ref>

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

OCA at 14:04, 6 November 2024

2024-11-06T14:04:55Z

← Older revision		Revision as of 14:04, 6 November 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7try]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TRY FirstGlance]. <br>		<table><tr><td colspan='2'>[[7try]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TRY FirstGlance]. <br>
	</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=7try FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7try OCA], [https://pdbe.org/7try PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7try RCSB], [https://www.ebi.ac.uk/pdbsum/7try PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7try ProSAT]</span></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]] 3.7Å</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=7try FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7try OCA], [https://pdbe.org/7try PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7try RCSB], [https://www.ebi.ac.uk/pdbsum/7try PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7try ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/CRFR2_HUMAN CRFR2_HUMAN] G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels.		[https://www.uniprot.org/uniprot/CRFR2_HUMAN CRFR2_HUMAN] G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The ability to couple with multiple G protein subtypes, such as G(s), G(i/o), or G(q/11), by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G(s) protein, have been determined. However, no structure of class B GPCRs with G(q/11) has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G(11) and G(o). We compare these structures with the structure of CRF2R in complex with G(s) to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.

			Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.,Zhao LH, Lin J, Ji SY, Zhou XE, Mao C, Shen DD, He X, Xiao P, Sun J, Melcher K, Zhang Y, Yu X, Xu HE Nat Commun. 2022 Nov 5;13(1):6670. doi: 10.1038/s41467-022-33851-3. PMID:36335102<ref>PMID:36335102</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7try" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Transducin 3D structures\|Transducin 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:22, 9 November 2022

2022-11-09T07:22:34Z

← Older revision		Revision as of 07:22, 9 November 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7try ~~is ON HOLD until Paper Publication~~		==Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein==
			<StructureSection load='7try' size='340' side='right'caption='[[7try]], [[Resolution\|resolution]] 3.70Å' scene=''>
	~~Authors~~: ~~Zhao~~, L.-H.~~, Lin, J~~., ~~Mao, C~~.~~, Zhou, X~~.E., Ji, S.~~, Shen, D~~.~~, Xiao, P~~., ~~Melcher, K~~.~~, Zhang, Y~~.~~, Yu, X~~., ~~Xu, H~~.E.		== Structural highlights ==
			<table><tr><td colspan='2'>[[7try]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TRY FirstGlance]. <br>
	~~Description~~: ~~Cryo~~-~~EM structure of~~ corticotropin releasing factor ~~receptor 2 bound~~ to ~~Urocortin 1 and coupled with heterotrimeric G11 protein~~		</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=7try FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7try OCA], [https://pdbe.org/7try PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7try RCSB], [https://www.ebi.ac.uk/pdbsum/7try PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7try ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
	[[Category: ~~Zhang, Y~~]]		== Function ==
	[[Category: ~~Zhou, X.E~~]]		[https://www.uniprot.org/uniprot/CRFR2_HUMAN CRFR2_HUMAN] G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels.
	[[Category: ~~Xu, H.E~~]]		__TOC__
	[[Category: ~~Yu, X~~]]		</StructureSection>
	[[Category: ~~Zhao, L.-H~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Lin, J~~]]		[[Category: Large Structures]]
	[[Category: Melcher, K]]		[[Category: Rattus norvegicus]]
	[[Category: Xiao, P]]		[[Category: Synthetic construct]]
	[[Category: ~~Shen, D~~]]		[[Category: Ji S]]
	[[Category: ~~Ji, S~~]]		[[Category: Lin J]]
	[[Category: ~~Mao, C~~]]		[[Category: Mao C]]
			[[Category: Melcher K]]
			[[Category: Shen D]]
			[[Category: Xiao P]]
			[[Category: Xu HE]]
			[[Category: Yu X]]
			[[Category: Zhang Y]]
			[[Category: Zhao L-H]]
			[[Category: Zhou XE]]

OCA at 03:43, 26 October 2022

2022-10-26T03:43:06Z

← Older revision		Revision as of 03:43, 26 October 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7try is ON HOLD		The entry 7try is ON HOLD until Paper Publication

	Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.		Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.
Line 14:		Line 14:
	[[Category: Lin, J]]		[[Category: Lin, J]]
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
			[[Category: Xiao, P]]
			[[Category: Shen, D]]
	[[Category: Ji, S]]		[[Category: Ji, S]]
	~~[[Category: Shen, D]]~~
	~~[[Category: Xiao, P]]~~
	[[Category: Mao, C]]		[[Category: Mao, C]]

OCA at 04:23, 28 September 2022

2022-09-28T04:23:42Z

← Older revision		Revision as of 04:23, 28 September 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7try is ON HOLD ~~until Paper Publication~~		The entry 7try is ON HOLD

	Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.		Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.

OCA at 05:30, 14 September 2022

2022-09-14T05:30:11Z

← Older revision		Revision as of 05:30, 14 September 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7try is ON HOLD		The entry 7try is ON HOLD until Paper Publication

	Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.		Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.
Line 14:		Line 14:
	[[Category: Lin, J]]		[[Category: Lin, J]]
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
			[[Category: Ji, S]]
			[[Category: Shen, D]]
	[[Category: Xiao, P]]		[[Category: Xiao, P]]
	~~[[Category: Shen, D]]~~
	~~[[Category: Ji, S]]~~
	[[Category: Mao, C]]		[[Category: Mao, C]]

OCA at 16:19, 27 July 2022

2022-07-27T16:19:02Z

← Older revision		Revision as of 16:19, 27 July 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7try is ON HOLD ~~until Paper Publication~~		The entry 7try is ON HOLD

	Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.		Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.

OCA at 14:52, 6 July 2022

2022-07-06T14:52:23Z

← Older revision		Revision as of 14:52, 6 July 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7try is ON HOLD		The entry 7try is ON HOLD until Paper Publication

	Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.		Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.

OCA at 03:50, 15 June 2022

2022-06-15T03:50:41Z

← Older revision		Revision as of 03:50, 15 June 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7try is ON HOLD ~~until Paper Publication~~		The entry 7try is ON HOLD

	Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.		Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.
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	Description: Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein		Description: Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Zhang, Y]]
	[[Category: Zhou, X.E]]		[[Category: Zhou, X.E]]
	[[Category: Xu, H.E]]		[[Category: Xu, H.E]]
	[[Category: Yu, X]]		[[Category: Yu, X]]
			[[Category: Zhao, L.-H]]
	[[Category: Lin, J]]		[[Category: Lin, J]]
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
			[[Category: Xiao, P]]
			[[Category: Shen, D]]
	[[Category: Ji, S]]		[[Category: Ji, S]]
	[[Category: Mao, C]]		[[Category: Mao, C]]
	~~[[Category: Zhang, Y]]~~
	~~[[Category: Zhao, L.-H]]~~
	~~[[Category: Xiao, P]]~~
	~~[[Category: Shen, D]]~~

OCA at 04:52, 9 March 2022

2022-03-09T04:52:46Z

← Older revision		Revision as of 04:52, 9 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7try is ON HOLD		The entry 7try is ON HOLD until Paper Publication

	Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.		Authors: Zhao, L.-H., Lin, J., Mao, C., Zhou, X.E., Ji, S., Shen, D., Xiao, P., Melcher, K., Zhang, Y., Yu, X., Xu, H.E.
Line 7:		Line 7:
	Description: Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein		Description: Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	~~[[Category: Zhang, Y]]~~
	[[Category: Zhou, X.E]]		[[Category: Zhou, X.E]]
	[[Category: Xu, H.E]]		[[Category: Xu, H.E]]
	[[Category: Yu, X]]		[[Category: Yu, X]]
	~~[[Category: Zhao, L.-H]]~~
	[[Category: Lin, J]]		[[Category: Lin, J]]
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
			[[Category: Ji, S]]
			[[Category: Mao, C]]
			[[Category: Zhang, Y]]
			[[Category: Zhao, L.-H]]
	[[Category: Xiao, P]]		[[Category: Xiao, P]]
	[[Category: Shen, D]]		[[Category: Shen, D]]
	~~[[Category: Ji, S]]~~
	~~[[Category: Mao, C]]~~