Structural highlights
Function
[TAM41_SCHPO] Catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid (PA) in the mitochondrial inner membrane. Required for the biosynthesis of the dimeric phospholipid cardiolipin, which stabilizes supercomplexes of the mitochondrial respiratory chain in the mitochondrial inner membrane.[UniProtKB:P53230]
Publication Abstract from PubMed
In mitochondria, CDP-diacylglycerol (CDP-DAG) is a crucial precursor for cardiolipin biosynthesis. Mitochondrial CDP-DAG is synthesized by the translocator assembly and maintenance protein 41 (Tam41) through an elusive process. Here we show that Tam41 adopts sequential catalytic mechanism, and report crystal structures of the bulk N-terminal region of Tam41 from Schizosaccharomyces pombe in the apo and CTP-bound state. The structure reveals that Tam41 contains a nucleotidyltransferase (NTase) domain and a winged helix domain. CTP binds to an "L"-shaped pocket sandwiched between the two domains. Rearrangement of a loop region near the active site is essential for opening the CTP-binding pocket. Docking of phosphatidic acid/CDP-DAG in the structure suggests a lipid entry/exit pathway connected to the "L"-shaped pocket. The C-terminal region of SpTam41 contains a positively charged amphipathic helix crucial for membrane association and participates in binding phospholipids. These results provide detailed insights into the mechanism of CDP-DAG biosynthesis in mitochondria.
Structures of the Mitochondrial CDP-DAG Synthase Tam41 Suggest a Potential Lipid Substrate Pathway from Membrane to the Active Site.,Jiao H, Yin Y, Liu Z Structure. 2019 May 14. pii: S0969-2126(19)30162-5. doi:, 10.1016/j.str.2019.04.017. PMID:31178220[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jiao H, Yin Y, Liu Z. Structures of the Mitochondrial CDP-DAG Synthase Tam41 Suggest a Potential Lipid Substrate Pathway from Membrane to the Active Site. Structure. 2019 May 14. pii: S0969-2126(19)30162-5. doi:, 10.1016/j.str.2019.04.017. PMID:31178220 doi:http://dx.doi.org/10.1016/j.str.2019.04.017
