8ZVQ

Cryo-EM Structure of Human Hormone-sensitive Lipase (HSL)

8ZVQ の概要

• エントリーDOI: 10.2210/pdb8zvq/pdb
• EMDBエントリー: 60512
• 分子名称: Hormone-sensitive lipase (1 entity in total)
• 機能のキーワード: lipid droplets, lipolysis, human hormone-sensitive lipase, hydrolysis of diacylglycerol (dag), hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 168436.45

構造登録者

Peng, H.,Xu, Q.,Wu, J.,Hu, Q. (登録日: 2024-06-11, 公開日: 2025-04-23)

主引用文献

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

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: 40221426
DOI: 10.1038/s41467-025-58887-z

実験手法

ELECTRON MICROSCOPY (3.4 Å)