Crystal structure of Tam41 cytidine diphosphate diacylglycerol synthase from a Firmicutes bacterium.

Translocator assembly and maintenance 41 (Tam41) catalyses the synthesis of cytidine diphosphate diacylglycerol (CDP-DAG), which is a high-energy intermediate phospholipid critical for generating cardiolipin in mitochondria. Although Tam41 is present almost exclusively in eukaryotic cells, a Firmicutes bacterium contains the gene encoding Tam41-type CDP-DAG synthase (FbTam41). FbTam41 converted phosphatidic acid (PA) to CDP-DAG using a ternary complex mechanism in vitro. Additionally, FbTam41 functionally substituted yeast Tam41 in vivo. These results demonstrate that Tam41-type CDP-DAG synthase functions in some prokaryotic cells. We determined the crystal structure of FbTam41 lacking the C-terminal 18 residues in the cytidine triphosphate (CTP)-Mg2+ bound form at a resolution of 2.6 Å. The crystal structure showed that FbTam41 contained a positively charged pocket that specifically accommodated CTP-Mg2+ and PA in close proximity. By using this structure, we constructed a model for the full-length structure of FbTam41 containing the last a-helix, which was missing in the crystal structure. Based on this model, we propose a molecular mechanism for CDP-DAG synthesis in bacterial cells and mitochondria. © The Author(s) 2022. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Citation

Keisuke Kimura, Fumihiro Kawai, Hisako Kubota-Kawai, Yasunori Watanabe, Kentaro Tomii, Rieko Kojima, Kunio Hirata, Yu Yamamori, Toshiya Endo, Yasushi Tamura. Crystal structure of Tam41 cytidine diphosphate diacylglycerol synthase from a Firmicutes bacterium. Journal of biochemistry. 2022 Mar 31;171(4):429-441

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PMID: 34964897

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