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A an amide bond amongst the
A an amide bond amongst the C-terminal carboxyl group and an amino group of EtN. Fatty chains of inositol phospholipids are inserted into the outer leaflet in the plasma membrane, when proteins are usually not straight inserted into the membrane (Fig. 1A). GPI anchor will be the only form of posttranslational modification by glycolipid. Much more than 150 various human proteins are GPI anchored (UniProt) (9). Functions of these GPI-anchoredThis work was partly supported by grants-in-aid from the National All-natural Science Foundation for Young Scientists of China (31400693) and the Natural Science Foundation of Jiangsu Province (BK20140141) (to M.F.). Manuscript received 30 August 2015 and in revised type 11 November 2015. Published, JLR Papers in Press, November 12, 2015 DOI 10.1194/jlr.RAbbreviations: Ace, angiotensin converting enzyme; AGPS, alkylglycerone phosphate synthase; ALP, alkaline phosphatase; BIQ, 1-[4butylbenzyl]isoquinoline; bkr, beaker; BST, bypass of Sec13; CHO, Chinese hamster ovary; DHAP-AT, dihydroxyacetone phosphate acyltransferase; Dol-P-Man, dolichol-phosphate-mannose; ER, endoplasmic reticulum; ERES, ER exit website; EtNP, ethanolamine phosphate; Gal, galactose; GalNAc, N-acetylgalactosamine; GlcN, non-N-acetylated glucosamine; GlcNAc, N-acetylglucosamine; GPI, glycosylphosphatidylinositol; GPIAP, glycosylphosphatidylinositol-anchored protein; HHAT, hedgehog acyltransferase; HPMRS, hyperphosphatasia with mental retardation syndrome; IPC, inositol-phospho-ceramide; Man, mannose; MBOAT, membrane bound O-acyl transferase; PI, phosphatidylinositol; PI-PLC, phosphatidylinositol-specific phospholipase PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/20065621 C; PLD, phospholipase D; RCDP, rhizomelic chondrodysplasia punctate; Ser, serine; Sia, sialic acid; SRP, signal recognition particle; TMD, transmembrane domain. 1 To whom correspondence should be addressed. e-mail: [email protected] 2016 by the American Society for Biochemistry and Molecular Biology, Inc.Journal of Lipid Analysis Volume 57,This article is readily available on the net at http://www.jlr.orgFig. 1. A: Frequent backbone of GPI anchors. The common backbone of GPI anchors, consisting of EtNP, 3 Mans, GlcN, and inositol phospholipid, is conserved in wide varieties of eukaryotes. The whole protein is anchored to the outer leaflet in the plasma membrane by fatty chains of inositol phospholipid. B: Dynamic adjustments from the PI moiety along biosynthesis of GPI-APs. The majority of the mammalian cellular PI and the first two GPI intermediates are diacyl types bearing sn2-linked unsaturated fatty acid. In contrast, the big types of mature GPI-APs around the cell surface have 1-alkyl-2-acyl PI bearing sn2-linked saturated fatty acid (ordinarily stearic acid). This structural distinction happens MedChemExpress LDC4297 throughout GPI-AP biosynthesis by means of two kinds of remodeling reactions, diacyl to diradyl remodeling in the ER and fatty acid remodeling in the Golgi. C: Mammalian GPI-APs. The very first Man within the popular core is ubiquitously modified by EtNP in the 2-position. In some proteins, the fourth Man is attached for the third Man. But in other proteins, the initial Man is modified by the 4GalNAc side branch, which may be elongated by 3Gal and Sia. Modified from Figure 1 in (197) with permission.proteins (GPI-APs) are different, such as >40 enzymes [alkaline phosphatases (ALPs), 5-nucleotidase, dipeptidase, and others], various adhesion molecules (contactins, glypicans, CD48, and other folks), receptors (folate receptors, GDNF receptor alphas, Fc RIIIb, and others), protease in.