View source for 8dha


==Leptin-bound leptin receptor complex- focused interaction==
<StructureSection load='8dha' size='340' side='right'caption='[[8dha]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dha]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DHA 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]] 3.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8dha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dha OCA], [https://pdbe.org/8dha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dha RCSB], [https://www.ebi.ac.uk/pdbsum/8dha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dha ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Leptin is an adipocyte-derived protein hormone that promotes satiety and energy homeostasis by activating the leptin receptor (LepR)-STAT3 signaling axis in a subset of hypothalamic neurons. Leptin signaling is dysregulated in obesity, however, where appetite remains elevated despite high levels of circulating leptin. To gain insight into the mechanism of leptin receptor activation, here we determine the structure of a stabilized leptin-bound LepR signaling complex using single particle cryo-EM. The structure reveals an asymmetric architecture in which a single leptin induces LepR dimerization via two distinct receptor-binding sites. Analysis of the leptin-LepR binding interfaces reveals the molecular basis for human obesity-associated mutations. Structure-based design of leptin variants that destabilize the asymmetric LepR dimer yield both partial and biased agonists that partially suppress STAT3 activation in the presence of wild-type leptin and decouple activation of STAT3 from LepR negative regulators. Together, these results reveal the structural basis for LepR activation and provide insights into the differential plasticity of signaling pathways downstream of LepR.

Structural insights into the mechanism of leptin receptor activation.,Saxton RA, Caveney NA, Moya-Garzon MD, Householder KD, Rodriguez GE, Burdsall KA, Long JZ, Garcia KC Nat Commun. 2023 Mar 31;14(1):1797. doi: 10.1038/s41467-023-37169-6. PMID:37002197<ref>PMID:37002197</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Caveney NA]]
[[Category: Garcia KC]]
[[Category: Saxton RA]]