8ERO
Structure of Xenopus cholinephosphotransferase1 in complex with CDP
Summary for 8ERO
Entry DOI | 10.2210/pdb8ero/pdb |
EMDB information | 28556 28557 |
Descriptor | Cholinephosphotransferase 1, MAGNESIUM ION, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, ... (4 entities in total) |
Functional Keywords | cdp-aps, phospholipid synthesis, transferase |
Biological source | Xenopus laevis (African clawed frog) |
Total number of polymer chains | 2 |
Total formula weight | 109750.01 |
Authors | |
Primary citation | Wang, L.,Zhou, M. Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis. Nat Commun, 14:2753-2753, 2023 Cited by 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: 37179328DOI: 10.1038/s41467-023-38003-9 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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