4Q2E

CRYSTAL STRUCTURE OF AN INTRAMEMBRANE CDP-DAG SYNTHETASE CENTRAL FOR PHOSPHOLIPID BIOSYNTHESIS (S200C/S258C, active mutant)

Summary for 4Q2E

• Entry DOI: 10.2210/pdb4q2e/pdb
• Related: 4Q2E
• Descriptor: Phosphatidate cytidylyltransferase, MERCURY (II) ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: intramembrane enzyme, cdsa fold, phospholipid biosynthesis lipid metabolism, ctp and phosphatidic acid binding, nucleotidyltransferase, membrane, transferase
• Biological source: Thermotoga maritima MSB8
• Cellular location: Cell membrane ; Multi-pass membrane protein : Q9X1B7
• Total number of polymer chains: 2
• Total formula weight: 65984.15

Authors

Liu, X.,Yin, Y.,Wu, J.,Liu, Z. (deposition date: 2014-04-08, release date: 2014-07-02, Last modification date: 2024-03-20)

Primary citation

Liu, X.,Yin, Y.,Wu, J.,Liu, Z.
Structure and mechanism of an intramembrane liponucleotide synthetase central for phospholipid biosynthesis
Nat Commun, 5:4244-4244, 2014

PubMed Abstract: Phospholipids are elemental building-block molecules for biological membranes. Biosynthesis of phosphatidylinositol, phosphatidylglycerol and phosphatidylserine requires a central liponucleotide intermediate named cytidine-diphosphate diacylglycerol (CDP-DAG). The CDP-DAG synthetase (Cds) is an integral membrane enzyme catalysing the formation of CDP-DAG, an essential step for phosphoinositide recycling during signal transduction. Here we report the structure of the Cds from Thermotoga maritima (TmCdsA) at 3.4 Å resolution. TmCdsA forms a homodimer and each monomer contains nine transmembrane helices arranged into a novel fold with three domains. An unusual funnel-shaped cavity penetrates half way into the membrane, allowing the enzyme to simultaneously accept hydrophilic substrate (cytidine 5'-triphosphate (CTP)/deoxy-CTP) from cytoplasm and hydrophobic substrate (phosphatidic acid) from membrane. Located at the bottom of the cavity, a Mg(2+)-K(+) hetero-di-metal centre coordinated by an Asp-Asp dyad serves as the cofactor of TmCdsA. The results suggest a two-metal-ion catalytic mechanism for the Cds-mediated synthesis of CDP-DAG at the membrane-cytoplasm interface.

PubMed: 24968740
DOI: 10.1038/ncomms5244

Experimental method

X-RAY DIFFRACTION (3.4 Å)