Identification of membrane O-acyltransferase family motifs |
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Authors: | Hideo Shindou Miki Eto Ryo Morimoto Takao Shimizu |
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Affiliation: | Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan |
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Abstract: | Cellular membranes contain several classes of glycerophospholipids, which have numerous structural and functional roles in cells. Membrane diversity and asymmetry are important for membrane fluidity, curvature, and storage of lipid mediator precursors. Using acyl-CoAs, glycerophospholipids are first formed in the de novo pathway (Kennedy pathway), and then modified in the remodeling pathway (Lands’ cycle) to generate mature membrane. Recently, several lysophospholipid acyltransferases (LPLATs) from two families, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family and the membrane bound O-acyltransferase (MBOAT) family, were shown to function in the remodeling pathway. The MBOAT family possesses either LPLAT activity or protein O-acyltransferase activity. While the motifs of the AGPAT family have been well characterized, the MBOAT motifs remain unclear. In this study, we identified four MBOAT motifs essential for LPLAT activities by extensive site-directed mutagenesis. These findings further our understanding of the enzyme reaction mechanisms and will contribute to structure predictions for the MBOAT family enzymes. |
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Keywords: | PAF, platelet-activating factor PA, phosphatidic acid PC, phosphatidylcholine PE, phosphatidylethanolamine PG, phosphatidylglycerol PI, phosphatidylinositol PS, phosphatidylserine CL, cardiolipin PLA2, phospholipase A2 LPLAT, lysophospholipid acyltransferase AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase MBOAT, membrane bound O-acyltransferase LPCAT, lyso-PC acyltransferase LPEAT, lyso-PE acyltransferase LPAAT, lyso-PA acyltransferase LPGAT, lyso-PG acyltransferase LCLAT1, lyso-CL acyltransferase l LPIAT, LPI acyltransferase LPSAT, lyso-PS acyltransferase CHO, Chinese hamster ovary |
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