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Elucidation of the cytosolic phospholipase A2‐α‐‐ceramide‐1‐phosphate binding site
Author(s) -
Olmstead Deborah Nicole,
Ward Katherine E,
Sudhahar Christopher G,
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.939.4
Subject(s) - phospholipase a2 , ceramide , arachidonic acid , biochemistry , lipid signaling , cytosol , sphingolipid , chemistry , biology , microbiology and biotechnology , enzyme , apoptosis
Cytosolic phospholipase A2‐alpha (cPLA 2 α) has been a protein of interest for over 16 years because of its presence in inflammatory diseases, including asthma and rheumatoid arthritis. cPLA 2 α is composed of two domains, a catalytic domain that generates arachidonic acid by cleaving phospholipids, and a C2 domain responsible for anchoring the protein to the lipid membrane. Ceramide‐1‐phosphate (C1P) is a sphingolipid found in inflamed tissue that previous research demonstrates to significantly upregulate the activity of cPLA 2 α. cPLA 2 α's C2 domain contains a debated binding site for C1P, and the goal of this study is to culture 15 N‐tagged cPLA 2 α C2 domain for structural investigation by NMR. In addition, binding studies utilizing large unilamellar vesicles (LUV) and increasing concentrations of C1P will help us construct a binding curve, thus better understand C2 binding to C1P. Preliminary results of the NMR study and LUV assay support our hypothesis that C1P and cPLA 2 α interact. This interaction is likely significant in inflammatory disease processes and is potentially a novel drug target. Funding provided by American Heart Association SDG0735350N.