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A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7
- Source :
- 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.
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 59
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....7faba9600e0ba307383cb1ae6b051424