دورية أكاديمية
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Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis.

التفاصيل البيبلوغرافية
العنوان: Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis.
المؤلفون: Wang L; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA. liew@bcm.edu., Zhou M; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA. mzhou@bcm.edu.
المصدر: Nature communications [Nat Commun] 2023 May 13; Vol. 14 (1), pp. 2753. Date of Electronic Publication: 2023 May 13.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Diacylglycerol Cholinephosphotransferase*/metabolism , Eukaryotic Cells*/metabolism, Cryoelectron Microscopy ; Phosphotransferases/metabolism ; Cytidine Diphosphate Choline/metabolism ; Phosphatidylcholines/metabolism ; Saccharomyces cerevisiae/metabolism ; Catalysis
مستخلص: Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic cell membranes. In eukaryotes, two highly homologous enzymes, cholinephosphotransferase-1 (CHPT1) and choline/ethanolamine phosphotransferase-1 (CEPT1) catalyze the final step of de novo PC synthesis. CHPT1/CEPT1 joins two substrates, cytidine diphosphate-choline (CDP-choline) and diacylglycerol (DAG), to produce PC, and Mg 2+ is required for the reaction. However, mechanisms of substrate recognition and catalysis remain unresolved. Here we report structures of a CHPT1 from Xenopus laevis (xlCHPT1) determined by cryo-electron microscopy to an overall resolution of ~3.2 Å. xlCHPT1 forms a homodimer, and each protomer has 10 transmembrane helices (TMs). The first 6 TMs carve out a cone-shaped enclosure in the membrane in which the catalysis occurs. The enclosure opens to the cytosolic side, where a CDP-choline and two Mg 2+ are coordinated. The structures identify a catalytic site unique to eukaryotic CHPT1/CEPT1 and suggest an entryway for DAG. The structures also reveal an internal pseudo two-fold symmetry between TM3-6 and TM7-10, and suggest that CHPT1/CEPT1 may have evolved from their distant prokaryotic ancestors through gene duplication.
(© 2023. The Author(s).)
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معلومات مُعتمدة: R01 DK122784 United States DK NIDDK NIH HHS; RM1 GM145416 United States GM NIGMS NIH HHS
المشرفين على المادة: EC 2.7.8.2 (Diacylglycerol Cholinephosphotransferase)
EC 2.7.- (Phosphotransferases)
536BQ2JVC7 (Cytidine Diphosphate Choline)
0 (Phosphatidylcholines)
تواريخ الأحداث: Date Created: 20230513 Date Completed: 20230515 Latest Revision: 20231119
رمز التحديث: 20231119
مُعرف محوري في PubMed: PMC10182977
DOI: 10.1038/s41467-023-38003-9
PMID: 37179328
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-38003-9