N-linked glycosylation-1课件.ppt

Glycobiology; ;“Hybrid”;The biosynthesis of N-glycans was elucidated in the 1960s and 1970s by using cell-free systems and lectin-resistant cell lines. N-glycan addition was noted to occur on asparagines in the sequence context Asn-X-Ser/Thr.;All eukaryotic cells produce N-glycans . N-linked glycosylation is the best understood route to protein glycosylation . The molecular cloning of vertebrate glycosyltransferase and glycosidase genes involved in N-glycan biosynthesis began in the 1980s and continues to the present .;;Manβ1;GLcNAc;Manβ1;Extracellular N-glycans in vertebrates exist as high-mannose ,hybrid, or complex subtypes;Hybrid structures are defined as those with both substituted (GlcNAc linkage) and unsubstituted mannose residues.;Complex N-glycans refer to those in with both the α3- and α6- linked mannose residues are substituted with GlcNAc moieties;High mannose N-glycans When total N-glycans are analyzed from various cells, most vertebrate extracellular N-glycans are found to be of the complex subtype.;Major Classes of N-Glycans;In forming multi-antennary N-glycan structures, GlcNAc residues may be added to the trimannosyl core by six different GlcNAc transferases(Ⅰ-Ⅵ ).;Bi-antennary;2.2 Assembly of N-linked glycans occurs in three major stages;2.3 The precursor oligosaccharide for N-linked glycans is assembled on the lipid dolichol;The dolichol oligosaccharide precursor consists of dolichol lipid bearing a pyrophosphate linkage to an oligosaccharide composed of 14 special monosaccharide linkage. The structure has been conserved among all eukaryotes. ;The donor that initiates N-linked glycan synthesis is a Glc3Man9GlcNAc2 structure attached to the lipid dolichol through a pyrophosphated linkage. （Fig.2.3）;This extended hydrophobic region is inserted into the lipid bilayer,possibly in a helical or folded conformation.;“Lipid-Linked Oligosaccharide” (LLO);御刮澡引锄痢瘫休质符挠吵旗氢戚漆墩养千傍掘炮嗣寿掖者酌蠢谣元侗朗N-linked glycosylation-1课件N-linked glycosylation-1课件;Evidence from