OCA at 06:26, 7 April 2023

2023-04-07T06:26:44Z

←Older revision		Revision as of 06:26, 7 April 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8avo is ~~ON HOLD until Paper~~ Publication	+	==Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric isoleucine GCN4 zipper (open 3:3 model).==
		+	<StructureSection load='8avo' size='340' side='right'caption='[[8avo]], [[Resolution\|resolution]] 6.84Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8avo]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AVO 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=8avo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8avo OCA], [https://pdbe.org/8avo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8avo RCSB], [https://www.ebi.ac.uk/pdbsum/8avo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8avo ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/LEP_HUMAN LEP_HUMAN] Defects in LEP may be a cause of obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9500540</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/LEP_HUMAN LEP_HUMAN] May function as part of a signaling pathway that acts to regulate the size of the body fat depot. An increase in the level of LEP may act directly or indirectly on the CNS to inhibit food intake and/or regulate energy expenditure as part of a homeostatic mechanism to maintain constancy of the adipose mass.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The adipokine Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight and exerts additional pleiotropic functions in immunity, fertility and cancer. However, the structure and mechanism of Leptin-mediated LEP-R assemblies has remained unclear. Intriguingly, the signaling-competent isoform of LEP-R is only lowly abundant amid several inactive short LEP-R isoforms contributing to a mechanistic conundrum. Here we show by X-ray crystallography and cryo-EM that, in contrast to long-standing paradigms, Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry and demonstrate such Leptin-induced trimerization of LEP-R on living cells via single-molecule microscopy. In mediating these assemblies, Leptin undergoes drastic restructuring that activates its site III for binding to the Ig domain of an adjacent LEP-R. These interactions are abolished by mutations linked to obesity. Collectively, our study provides the structural and mechanistic framework for how evolutionarily conserved Leptin:LEP-R assemblies with 3:3 stoichiometry can engage distinct LEP-R isoforms to achieve signaling.

-	~~Authors~~:	+	Mechanism of receptor assembly via the pleiotropic adipokine Leptin.,Tsirigotaki A, Dansercoer A, Verschueren KHG, Markovic I, Pollmann C, Hafer M, Felix J, Birck C, Van Putte W, Catteeuw D, Tavernier J, Fernando Bazan J, Piehler J, Savvides SN, Verstraete K Nat Struct Mol Biol. 2023 Mar 23. doi: 10.1038/s41594-023-00941-9. PMID:36959263<ref>PMID:36959263</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8avo" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Savvides SN]]
		+	[[Category: Tsirigotaki A]]
		+	[[Category: Verschueren KG]]
		+	[[Category: Verstraete K]]

OCA at 16:38, 19 October 2022

2022-10-19T16:38:39Z

←Older revision		Revision as of 16:38, 19 October 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

2022-09-07T15:24:22Z

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

←Older revision

Revision as of 15:24, 7 September 2022

OCA: New page: '''Unreleased structure''' The entry 8avo is ON HOLD Authors: Description: Category: Unreleased Structures

2022-09-07T15:24:21Z

New page: '''Unreleased structure''' The entry 8avo is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8avo is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8avo - Revision history

OCA at 06:26, 7 April 2023

OCA at 16:38, 19 October 2022

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

OCA: New page: '''Unreleased structure''' The entry 8avo is ON HOLD Authors: Description: Category: Unreleased Structures