8UL9

Cholinephosphotransferase in complex with diacylglycerol

Summary for 8UL9

• Entry DOI: 10.2210/pdb8ul9/pdb
• EMDB information: 42357
• Descriptor: Cholinephosphotransferase 1, MAGNESIUM ION, 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (5 entities in total)
• Functional Keywords: lipid metabolism, phospholipid synthesis, membrane protein enzyme, choline metabolism, membrane protein
• Biological source: Saccharomyces cerevisiae (brewer's yeast)
• Total number of polymer chains: 2
• Total formula weight: 94364.54

Authors

Roberts, J.R.,Maeda, S.,Ohi, M.D. (deposition date: 2023-10-16, release date: 2024-10-23, Last modification date: 2025-01-15)

Primary citation

Roberts, J.R.,Horibata, Y.,Kwarcinski, F.E.,Lam, V.,Raczkowski, A.M.,Hubbard, A.,White, B.,Sugimoto, H.,Tall, G.G.,Ohi, M.D.,Maeda, S.
Structural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase.
Nat Commun, 16:111-111, 2025

PubMed Abstract: Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5'-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) that are the main phospholipids in eukaryotic cells. Here we present the structure of the yeast CPT1 in multiple substrate-bound states. Structural and functional analysis of these binding-sites reveal the critical residues for the DAG acyl-chain preference and the choline/ethanolamine selectivity. Additionally, we present the structure in complex with a potent inhibitor characterized in this study. The ensemble of structures allows us to propose the reaction mechanism for phospholipid biosynthesis by the family of CDP-alcohol phosphotransferases (CDP-APs).

PubMed: 39747155
DOI: 10.1038/s41467-024-55673-1

Experimental method

ELECTRON MICROSCOPY (3.2 Å)