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The Molecular Basis of Ceramide‐1‐Phosphate Recognition by Peripheral Proteins
Author(s) -
Ward Katherine Elizabeth,
Sudhahar Christopher G.,
Olmstead Deborah N.,
Stahelin Robert V.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.939.11
Subject(s) - lipid signaling , microbiology and biotechnology , sphingolipid , ceramide , cytosol , phospholipase a2 , arachidonic acid , biochemistry , biology , hydroxyeicosatetraenoic acid , inflammation , phospholipase d , chemistry , signal transduction , enzyme , apoptosis , immunology
The sphingolipid ceramide‐1‐phosphate (C1P) plays a critical role in the cellular signaling that mediates inflammation, cell proliferation and phagocytosis. C1P has been shown to increase the activity of cytosolic phospholipase A 2 α (cPLA 2 α) as well regulate its translocation to cellular membranes, a process that promotes inflammation through the production of arachidonic acid. In this study we have resolved the first C1P binding site of a peripheral protein. Using NMR we demonstrate the cPLA 2 α C2 domain interaction site for C1P by mapping chemical shifts. Subsequently, this novel‐binding site is confirmed with in vitro biophysical and biochemical analysis as well as molecular dynamics simulations. To search the human genome for other C1P binding proteins we have performed proteomic studies to began high throughput characterization of the conserved nature of C1P binding. Funding source: American Heart Association SDG0735350N (R.V.S)