دورية أكاديمية
Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis.
العنوان: | Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis. |
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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 |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-023-38003-9 |