8ZVQ
Cryo-EM Structure of Human Hormone-sensitive Lipase (HSL)
Summary for 8ZVQ
| Entry DOI | 10.2210/pdb8zvq/pdb |
| EMDB information | 60512 |
| Descriptor | Hormone-sensitive lipase (1 entity in total) |
| Functional Keywords | lipid droplets, lipolysis, human hormone-sensitive lipase, hydrolysis of diacylglycerol (dag), hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 168436.45 |
| Authors | |
| Primary citation | Peng, H.,Xu, Q.,Zhang, T.,Zhu, J.,Pan, J.,Guan, X.,Feng, S.,Wu, J.,Hu, Q. Molecular determinants for the association of human hormone-sensitive lipase with lipid droplets. Nat Commun, 16:3497-3497, 2025 Cited by PubMed Abstract: 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 Å. 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. PubMed: 40221426DOI: 10.1038/s41467-025-58887-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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