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Updated: Jul 31, 2025
09:33
In Vitro Assay to Measure Phosphatidylethanolamine Methyltransferase Activity
Published on: January 5, 2016
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Structural basis for catalysis of human choline/ethanolamine phosphotransferase 1
Zhenhua Wang1, Meng Yang1, Yufan Yang1
1The First Affiliated Hospital of USTC, MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
Nature Communications
|May 3, 2023
Summary
This study reveals the cryo-electron microscopy structures of human CEPT1, a key enzyme in synthesizing phosphatidylcholine (PC) and phosphatidylethanolamine) (PE). Findings suggest a substrate-triggered mechanism for product release during lipid biosynthesis.
Area of Science:
- Biochemistry
- Structural Biology
- Cell Biology
Background:
- Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are crucial eukaryotic membrane lipids involved in various cellular processes.
- Choline/ethanolamine phosphotransferase 1 (CEPT1) is essential for PC and PE biosynthesis via the Kennedy pathway.
Purpose of the Study:
- To determine the high-resolution cryo-electron microscopy (cryo-EM) structures of human CEPT1.
- To elucidate the structural basis of CEPT1's catalytic mechanism and substrate interaction.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to obtain structures of human CEPT1.
- Structures were determined for both the apoenzyme and its complex with CDP-choline.
- Biochemical characterizations were performed to support structural observations.
Main Results:
- The cryo-EM structures of human CEPT1 were resolved at 3.7 Å and 3.8 Å.
- CEPT1 forms a dimer, with each protomer containing 10 transmembrane segments.
- A conserved catalytic domain features a hydrophobic chamber that likely coordinates acyl tails during catalysis.
- A PC-like density within the chamber disappeared upon CDP-choline binding, suggesting a product release mechanism.
Conclusions:
- The structures provide unprecedented insight into the mechanism of PC and PE biosynthesis by CEPT1.
- A substrate-triggered product release mechanism is proposed based on structural observations.
- These findings advance our understanding of membrane lipid metabolism and its regulation.
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