View source for 8zvq


==Cryo-EM Structure of Human Hormone-sensitive Lipase (HSL)==
<StructureSection load='8zvq' size='340' side='right'caption='[[8zvq]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zvq]] is a 2 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=8ZVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZVQ 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]] 3.4&#8491;</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=8zvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zvq OCA], [https://pdbe.org/8zvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zvq RCSB], [https://www.ebi.ac.uk/pdbsum/8zvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zvq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/LIPS_HUMAN LIPS_HUMAN] LIPE-related familial partial lipodystrophy. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/LIPS_HUMAN LIPS_HUMAN] Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters (PubMed:15716583, PubMed:15955102, PubMed:19800417, PubMed:8812477). Shows a preferential hydrolysis of DAGs over TAGs and MAGs and preferentially hydrolyzes the fatty acid (FA) esters at the sn-3 position of the glycerol backbone in DAGs (PubMed:19800417). Preferentially hydrolyzes FA esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs (By similarity). Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (By similarity). In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production (By similarity).[UniProtKB:P15304][UniProtKB:P54310]<ref>PMID:15716583</ref> <ref>PMID:15955102</ref> <ref>PMID:19800417</ref> <ref>PMID:8812477</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lipid droplets (LDs) are the main cellular storage sites for triacylglycerols (TAGs), playing an important role in energy homeostasis and cell signaling. Hydrolysis of the stored TAGs begins with conversion of TAGs into diacylglycerols (DAGs) by adipose triglyceride lipase (ATGL), followed by hydrolysis of DAGs by hormone-sensitive lipase (HSL). Despite the central role of HSL in lipolysis, the molecular determinants for its LD association have remained elusive. Here, we report the cryo-EM structure of human HSL at 3.4 A. Combining this with hydrogen-deuterium exchange mass spectrometry, biochemical and cellular assays, we identify residues 489-538, referred to as the "H-motif", and the N-terminal 4-helix bundle of HSL as LD-binding motifs mediating direct interaction of HSL with LDs. LD binding mediated by the LD-binding motifs is independent of HSL phosphorylation catalyzed by the cAMP-dependent kinase PKA. Our findings provide insight into the LD binding mechanism of HSL, advancing our understanding of the regulation of lipolysis.

Molecular determinants for the association of human hormone-sensitive lipase with lipid droplets.,Peng H, Xu Q, Zhang T, Zhu J, Pan J, Guan X, Feng S, Wu J, Hu Q Nat Commun. 2025 Apr 12;16(1):3497. doi: 10.1038/s41467-025-58887-z. PMID:40221426<ref>PMID:40221426</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8zvq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hu Q]]
[[Category: Peng H]]
[[Category: Wu J]]
[[Category: Xu Q]]