Cryo-EM structure of human lipid phosphate phosphatase 2
Wanyi Wang1, Yue Xu2, Peilin Guo2
1State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Center for Life and Medical Sciences, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, Hubei 430071, China; Hubei Province Key Laboratory of Allergy and Immunology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, Hubei 430071, China.
None:
Lipid phosphate phosphatases (LPPs) dephosphorylate lipid phosphates to regulate signaling and metabolism. Among the three mammalian isoforms, LPP1, LPP2, and LPP3, LPP2 has been strongly associated with cancer, making it a potential therapeutic target. However, the molecular mechanisms underlying its structural organization, substrate recognition, and catalysis remain elusive. Here, we report the cryo-EM structure of human LPP2 (hLPP2). hLPP2 assembles as a homo-tetramer, with phosphatidylcholine bound in the substrate pocket. The tetrameric arrangement provides a structural basis for LPP oligomerization. The wide, open-ended substrate pocket explains the enzyme's broad substrate specificity. Structural comparison with PAP2 family members, including hG6PC1 and ecPgpB, suggests a conserved catalytic mechanism and highlights the regulatory role of residue E159 in stabilizing the catalytic center and phosphate release. Collectively, these findings advance our understanding of the structural basis and enzymatic mechanism of LPPs and may provide insights for the development of novel cancer therapies.
More Related Videos
07:26Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
Published on: October 15, 2016
13:34Production, Crystallization and Structure Determination of C. difficile PPEP-1 via Microseeding and Zinc-SAD
Published on: December 30, 2016
Related Concept Videos
Cryo-electron Microscopy
Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Asymmetric Lipid Bilayer
Assembly of the Lipid Bilayer in the ER
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
Membrane Fluidity
Membrane Fluidity
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
