A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7
| العنوان: | A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7 |
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| المؤلفون: | Bockelmann, Svenja, Mina, John G M, Korneev, Sergei, Hassan, Dina G, Mueller, Dagmar, Hilderink, Angelika, Vlieg, Hedwich C, Raijmakers, Reinout, Heck, Albert J R, Haberkant, Per, Holthuis, Joost C M, Biomolecular Mass Spectrometry and Proteomics, Crystal and Structural Chemistry, Sub Crystal and Structural Chemistry, Sub Biomol.Mass Spectrometry & Proteom., Afd Biomol.Mass Spect. and Proteomics |
| المساهمون: | Biomolecular Mass Spectrometry and Proteomics, Crystal and Structural Chemistry, Sub Crystal and Structural Chemistry, Sub Biomol.Mass Spectrometry & Proteom., Afd Biomol.Mass Spect. and Proteomics |
| المصدر: | Journal of Lipid Research, Vol 59, Iss 3, Pp 515-530 (2018) Journal of Lipid Research, 59(3), 515. American Society for Biochemistry and Molecular Biology Inc. |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Ceramide, STARD7, Ceramide binding, QD415-436, Ceramides, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, Humans, Binding site, phosphatidylcholine, Research Articles, Ceramide Transfer Protein, steroidogenic acute regulatory protein D7, Photoaffinity labeling, Steroidogenic acute regulatory protein, Cell Biology, lipid transfer protein, Lipids, Cell biology, mitochondria, ceramide transfer protein, 030104 developmental biology, chemistry, click chemistry, Carrier Proteins, Plant lipid transfer proteins, ceramidetransfer protein, photoaffinity labeling, HeLa Cells |
| الوصف: | Ceramides are central intermediates of sphingolipid metabolism with dual roles as mediators of cellular stress signaling and mitochondrial apoptosis. How ceramides exert their cytotoxic effects is unclear and their poor solubility in water hampers a search for specific protein interaction partners. Here, we report the application of a photoactivatable and clickable ceramide analog, pacCer, to identify ceramide binding proteins and unravel the structural basis by which these proteins recognize ceramide. Besides capturing ceramide transfer protein (CERT) from a complex proteome, our approach yielded CERT-related steroidogenic acute regulatory protein D7 (StarD7) as novel ceramide binding protein. Previous work revealed that StarD7 is required for efficient mitochondrial import of phosphatidylcholine (PC) and serves a critical role in mitochondrial function and morphology. Combining site-directed mutagenesis and photoaffinity labeling experiments, we demonstrate that the steroidogenic acute regulatory transfer domain of StarD7 harbors a common binding site for PC and ceramide. While StarD7 lacks robust ceramide transfer activity in vitro, we find that its ability to shuttle PC between model membranes is specifically affected by ceramides. Besides demonstrating the suitability of pacCer as a tool to hunt for ceramide binding proteins, our data point at StarD7 as a candidate effector protein by which ceramides may exert part of their mitochondria-mediated cytotoxic effects. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0022-2275 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7faba9600e0ba307383cb1ae6b051424Test http://www.sciencedirect.com/science/article/pii/S0022227520331394Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7faba9600e0ba307383cb1ae6b051424 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222275 |
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