GPI-ANCHORED AND TRANSMEMBRANE-ANCHORED INFLUENZA HEMAGGLUTININ DIFFER IN STRUCTURE AND RECEPTOR-BINDING ACTIVITY

被引:91
作者
KEMBLE, GW
HENIS, YI
WHITE, JM
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT PHARMACOL,SAN FRANCISCO,CA 94143
[2] TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT BIOCHEM,IL-69978 TEL AVIV,ISRAEL
[3] UNIV CALIF SAN FRANCISCO,CELL BIOL PROGRAM,SAN FRANCISCO,CA 94143
关键词
D O I
10.1083/jcb.122.6.1253
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We investigated the influence of a glycosylphosphatidylinositol (GPI) anchor on the ectodomain of the influenza hemagglutinin (HA) by replacing the wild type (wt) transmembrane and cytoplasmic domains with a GPI lipid anchor. GPI-anchored HA (GPI-HA) was transported to the cell surface with equal efficiency and at the same rate as wt-HA. Like wt-HA, cell surface GPI-HA, and its ectodomain released with the enzyme PI-phospholipase C (PI-PLC), were 9S trimers. Compared to wt-HA, the GPI-HA ectodomain underwent additional terminal oligosaccharide modifications; some of these occurred near the receptor binding pocket and completely inhibited the ability of GPI-HA to bind erythrocytes. Growth of GPI-HA-expressing cells in the presence of the mannosidase I inhibitor deoxymannojirimycin (dMM) abrogated the differences in carbohydrate modification and restored the ability of GPI-HA to bind erythrocytes. The ectodomain of GPI-HA produced from cells grown in the presence or absence of dMM underwent characteristic low pH-induced conformational changes (it released its fusion peptides and became hydrophobic and proteinase sensitive) but at 0.2 and 0.4 pH units higher than wt-HA, respectively. These results demonstrate that although GPI-HA forms a stable trimer with characteristics of the wt, its structure is altered such that its receptor binding activity is abolished. Our results show that transmembrane and GPI-anchored forms of the same ectodomain can exhibit functionally important differences in structure at a great distance from the bilayer.
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页码:1253 / 1265
页数:13
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