8jis - Revision history

OCA at 12:01, 8 November 2023

OCA — Wed, 08 Nov 2023 12:01:50 GMT

←Older revision		Revision as of 12:01, 8 November 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8jis is ~~ON HOLD until Paper~~ Publication	+	==Cryo-EM structure of the GLP-1R/GCGR dual agonist peptide15-bound human GLP-1R-Gs complex==
		+	<StructureSection load='8jis' size='340' side='right'caption='[[8jis]], [[Resolution\|resolution]] 2.46Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8jis]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [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=8JIS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JIS 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]] 2.46Å</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=8jis FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jis OCA], [https://pdbe.org/8jis PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jis RCSB], [https://www.ebi.ac.uk/pdbsum/8jis PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jis ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GBB1_RAT GBB1_RAT] 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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR), two members of class B1 G protein-coupled receptors, play important roles in glucose homeostasis and energy metabolism. They share a high degree of sequence homology but have different functionalities. Unimolecular dual agonists of both receptors developed recently displayed better clinical efficacies than that of monotherapy. To study the underlying molecular mechanisms, we determined high-resolution cryo-electron microscopy structures of GLP-1R or GCGR in complex with heterotrimeric G(s) protein and three GLP-1R/GCGR dual agonists including peptide 15, MEDI0382 (cotadutide) and SAR425899 with variable activating profiles at GLP-1R versus GCGR. Compared with related structures reported previously and supported by our published pharmacological data, key residues responsible for ligand recognition and dual agonism were identified. Analyses of peptide conformational features revealed a difference in side chain orientations within the first three residues, indicating that distinct engagements in the deep binding pocket are required to achieve receptor selectivity. The middle region recognizes extracellular loop 1 (ECL1), ECL2, and the top of transmembrane helix 1 (TM1) resulting in specific conformational changes of both ligand and receptor, especially the dual agonists reshaped ECL1 conformation of GLP-1R relative to that of GCGR, suggesting an important role of ECL1 interaction in executing dual agonism. Structural investigation of lipid modification showed a better interaction between lipid moiety of MEDI0382 and TM1-TM2 cleft, in line with its increased potency at GCGR than SAR425899. Together, the results provide insightful information for the design and development of improved therapeutics targeting these two receptors simultaneously.

-	~~Authors: Yang, L~~., Zhou, Q~~.T.~~, Dai, A~~.T.~~, Zhao, F~~.H.~~, Chang, R~~.L.~~, Ying, T~~.L.~~, Wu, B~~.L.~~, Yang, D~~.H.~~, Wang, M.W., ~~Cong, Z~~.T.	+	Structural analysis of the dual agonism at GLP-1R and GCGR.,Li Y, Zhou Q, Dai A, Zhao F, Chang R, Ying T, Wu B, Yang D, Wang MW, Cong Z Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2303696120. doi: , 10.1073/pnas.2303696120. Epub 2023 Aug 7. PMID:37549266<ref>PMID:37549266</ref>

-	~~Description: Cryo-EM structure~~ of the ~~GLP-1R~~/~~GCGR dual agonist peptide15~~-~~bound human GLP~~-~~1R-Gs complex~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Dai, A.T~~]]	+	<div class="pdbe-citations 8jis" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Wu, B.L~~]]	+	== References ==
-	[[Category: Chang~~, R.L~~]]	+	<references/>
-	[[Category: ~~Zhao, F.H~~]]	+	__TOC__
-	[[Category: ~~Zhou, Q.T~~]]	+	</StructureSection>
-	[[Category: Wang~~, M.W~~]]	+	[[Category: Bos taurus]]
-	[[Category: ~~Yang, L~~]]	+	[[Category: Escherichia coli]]
-	[[Category: Yang~~, D.H~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Cong, Z.T~~]]	+	[[Category: Large Structures]]
-	[[Category: Ying~~, T.L~~]]	+	[[Category: Rattus norvegicus]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Chang RL]]
		+	[[Category: Cong ZT]]
		+	[[Category: Dai AT]]
		+	[[Category: Wang MW]]
		+	[[Category: Wu BL]]
		+	[[Category: Yang DH]]
		+	[[Category: Yang L]]
		+	[[Category: Ying TL]]
		+	[[Category: Zhao FH]]
		+	[[Category: Zhou QT]]

OCA at 10:33, 1 November 2023

OCA — Wed, 01 Nov 2023 10:33:38 GMT

←Older revision		Revision as of 10:33, 1 November 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8jis is ON HOLD	+	The entry 8jis is ON HOLD until Paper Publication

	Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T.		Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T.
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	[[Category: Zhou, Q.T]]		[[Category: Zhou, Q.T]]
	[[Category: Wang, M.W]]		[[Category: Wang, M.W]]
-	[[Category: Yang, D.H]]
	[[Category: Yang, L]]		[[Category: Yang, L]]
		+	[[Category: Yang, D.H]]
	[[Category: Cong, Z.T]]		[[Category: Cong, Z.T]]
	[[Category: Ying, T.L]]		[[Category: Ying, T.L]]

OCA at 04:14, 6 September 2023

OCA — Wed, 06 Sep 2023 04:14:32 GMT

←Older revision		Revision as of 04:14, 6 September 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8jis is ON HOLD ~~until Paper Publication~~	+	The entry 8jis is ON HOLD

	Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T.		Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T.

-	Description: Cryo-EM structure of the GLP-1R/GCGR dual agonist ~~peptide 15~~-bound human GLP-1R-Gs complex	+	Description: Cryo-EM structure of the GLP-1R/GCGR dual agonist peptide15-bound human GLP-1R-Gs complex
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Dai, A.T]]		[[Category: Dai, A.T]]

OCA at 03:56, 5 July 2023

OCA — Wed, 05 Jul 2023 03:56:42 GMT

←Older revision		Revision as of 03:56, 5 July 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8jis is ON HOLD	+	The entry 8jis is ON HOLD until Paper Publication

	Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T.		Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T.

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

OCA — Wed, 07 Jun 2023 04:14:43 GMT

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

←Older revision

Revision as of 04:14, 7 June 2023

OCA: New page: '''Unreleased structure''' The entry 8jis is ON HOLD Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T. Descrip...

OCA — Wed, 07 Jun 2023 04:14:42 GMT

New page: '''Unreleased structure''' The entry 8jis is ON HOLD Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T. Descrip...

New page

'''Unreleased structure'''

The entry 8jis is ON HOLD

Authors: Yang, L., Zhou, Q.T., Dai, A.T., Zhao, F.H., Chang, R.L., Ying, T.L., Wu, B.L., Yang, D.H., Wang, M.W., Cong, Z.T.

Description: Cryo-EM structure of the GLP-1R/GCGR dual agonist peptide 15-bound human GLP-1R-Gs complex
[[Category: Unreleased Structures]]
[[Category: Dai, A.T]]
[[Category: Wu, B.L]]
[[Category: Chang, R.L]]
[[Category: Zhao, F.H]]
[[Category: Zhou, Q.T]]
[[Category: Wang, M.W]]
[[Category: Yang, D.H]]
[[Category: Yang, L]]
[[Category: Cong, Z.T]]
[[Category: Ying, T.L]]