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Identification of a common motif for the recognition of moieties containing polyunsaturated fatty acids
Author(s) -
Shulga Yulia V,
Topham Matthew K,
Epand Richard M
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.939.7
Subject(s) - gene isoform , biochemistry , enzyme , diacylglycerol kinase , phosphatidic acid , chemistry , isozyme , phosphatidylinositol , residue (chemistry) , kinase , gene , phospholipid , protein kinase c , membrane
The pattern of residues L/I‐X (2–4) ‐R‐X (2) ‐L‐X (3–4) ‐G, in which ‐X (n) ‐ represents n residues of any amino acids, is found in several enzymes acting on polyunsaturated fatty acids. For enzymes that do exhibit preference for polyunsaturated fatty acid‐containing lipids, generally only one isoform has this specificity and it is also the only isoform with this motif. One example we study is diacylglycerol kinase epsilon (DGKε). It is the only one of the 10 mammalian isoforms of DGK that exhibits arachidonoyl specificity and is the only isoform with the above motif. Mutations of the essential residues in this motif result in loss of arachidonoyl specificity. Furthermore, DGKα can be converted to an enzyme having this motif by substituting only one residue. When DGKα was mutated to gain the motif, the enzyme also gained some arachidonoyl specificity. This motif is also present in an isoform of phosphatidylinositol‐4‐phosphate‐5‐kinase (PIP5K) that we showed had arachidonoyl specificity for its substrate. Single residue mutations within the motif of this isoform result in loss of activity against an arachidonoyl substrate. We also demonstrate the importance of acyl chain specificity for the phosphatidic acid activation of PIP5K, and that this activation is dependent on the substrate. This is the first demonstration of a motif that endows specificity for an acyl chain.