8ERP

Structure of Xenopus cholinephosphotransferase1 in complex with CDP-choline

8ERP の概要

• エントリーDOI: 10.2210/pdb8erp/pdb
• EMDBエントリー: 28556 28557
• 分子名称: Cholinephosphotransferase 1, MAGNESIUM ION, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, ... (4 entities in total)
• 機能のキーワード: cdp-aps, phospholipid synthesis, transferase
• 由来する生物種: Xenopus laevis (African clawed frog)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 105359.85

構造登録者

Wang, L.,Zhou, M. (登録日: 2022-10-12, 公開日: 2023-04-26, 最終更新日: 2025-05-14)

主引用文献

Wang, L.,Zhou, M.
Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis.
Nat Commun, 14:2753-2753, 2023

PubMed Abstract: Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic cell membranes. In eukaryotes, two highly homologous enzymes, cholinephosphotransferase-1 (CHPT1) and choline/ethanolamine phosphotransferase-1 (CEPT1) catalyze the final step of de novo PC synthesis. CHPT1/CEPT1 joins two substrates, cytidine diphosphate-choline (CDP-choline) and diacylglycerol (DAG), to produce PC, and Mg is required for the reaction. However, mechanisms of substrate recognition and catalysis remain unresolved. Here we report structures of a CHPT1 from Xenopus laevis (xlCHPT1) determined by cryo-electron microscopy to an overall resolution of ~3.2 Å. xlCHPT1 forms a homodimer, and each protomer has 10 transmembrane helices (TMs). The first 6 TMs carve out a cone-shaped enclosure in the membrane in which the catalysis occurs. The enclosure opens to the cytosolic side, where a CDP-choline and two Mg are coordinated. The structures identify a catalytic site unique to eukaryotic CHPT1/CEPT1 and suggest an entryway for DAG. The structures also reveal an internal pseudo two-fold symmetry between TM3-6 and TM7-10, and suggest that CHPT1/CEPT1 may have evolved from their distant prokaryotic ancestors through gene duplication.

PubMed: 37179328
DOI: 10.1038/s41467-023-38003-9

実験手法

ELECTRON MICROSCOPY (3.7 Å)