title: Structure and mechanism of an intramembrane liponucleotide synthetase central for phospholipid biosynthesis.
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.
authors: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China [2].
authors: Xiuying
authors: X
authors: Liu
authors: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China [3].
authors: Yan
authors: Y
authors: Yin
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
authors: Jinjun
authors: J
authors: Wu
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
authors: Zhenfeng
authors: Z
authors: Liu
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002412:Cations; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis*; D011188:Potassium / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020124:Thermotoga maritima / Q000378:metabolism* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D002412:Cations; D010743:Phospholipids; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase; D008274:Magnesium; D011188:Potassium