《糖生物学》课程教学课件（讲稿）11 N-glycosylation and mucin

1. N-linked glycosylation

1.#N%linked#glycosyla2on#

Learning objectives. The structures of different classes of N-linkedglycans. Chemical steps in the biosynthesis of N-linkedglycans. the cellular compartmentalization biosyntheticsteps: The nature and causes of heterogeneity of N.linked glycans

Learning#objec2ves# • The#structures#of#different#classes#of#N%linked# glycans • Chemical#steps#in#the#biosynthesis#of#N%linked# glycans • the#cellular#compartmentaliza2on#biosynthe2c# steps# • The#nature#and#causes#of#heterogeneity#of#N% linked#glycans

: The N-linked glycosylation pathway is the bestunderstood route to protein glycosylation.. This pathway can be used to illustrate generalprinciples of glycoconjugate structure andbiosynthesis.: The nature of the N-linked glycosylationpathway also provides some insight into thefunctions and evolutionary history

• The#N%linked#glycosyla2on#pathway#is#the#best# understood#route#to#protein#glycosyla2on.# • This#pathway#can#be#used#to#illustrate#general# principles#of#glycoconjugate#structure#and# biosynthesis.# • The#nature#of#the#N%linked#glycosyla2on# pathway#also#provides#some#insight#into#the# func2ons#and#evolu2onary#history#

1.1 Diverse N-linked glycans have acommoncorestructure

1.1 Diverse N-linked glycans have a common core structure

Asparagine(Asn)GlcNAcOHresidueinpolypeptideHCH2H.ONH0IHOGlcNAcβ1-AsnNH-C-CH2-CHHOBHNHH1C=OHC=OHighmannoseManaα1-2Manα16Mana1ManB1-4GlcNAcβ1-4GlcNAcβ1-AsnMang1-2Mang12Mana1Manα1-2Manα1Complex:bi-antennaryNeuAcα2-6Galβ1-4GlcNAcβ1-2Manα16Manβ1-4GlcNAcβ1-4GlcNAcβ1-Asn3NeuAcα2-6Galβ1-4GlcNAcβ1-2Manα1

GlcNAcβ1%Asn#

1.2 Assembly of N-linked glycans occursin three major stages

1.2 Assembly of N-linked glycans occurs in three major stages

Three stages.Formationofalipid-linkedprecursoroligosaccharideen bloc (总的)transfer of the oligosaccharide tothe polypeptideProcessing of the oligosaccharide

Three#stages# • Forma2on#of#a#lipid%linked#precursor# oligosaccharide# • en#bloc#(总的)#transfer#of#the#oligosaccharide#to# the#polypep2de# • Processing#of#the#oligosaccharide#

3ProcessingInitial trimming ofAddition ofterminalsugarresiduessugarresiduesSecretion ordeliverytoplasmamembraneTrimmingandmodificationofbranchstructure2EnbloctransfertoproteinProteinsynthesis1Synthesisoflipid-linkedprecursoroligosaccharidePlasmaGolgi apparatusMembraneEndoplasmicreticulum

1.3 The precursor oligosaccharide for N-linked glycans is assembled on the lipiddolichol

1.3 The precursor oligosaccharide for N￾linked glycans is assembled on the lipid dolichol

A dolichol sugar that can serve as the donor inglycosyltransferaserxnsontheluminal（腔的）sideoftheendoplasmicreticulum（内质网）membrane.OHDolicholO=HO-P-OHOHOoGlucose15-19IsopreneunitHydrophobic portionof this lipidisfarlongerthanthefatty acid tails on membrane phospholipidsPossiblyinahelicalorfoldedconformation

A dolichol sugar that can serve as the donor in glycosyltransferase rxns on the luminal (腔的) side of the endoplasmic reticulum (内质网) membrane Hydrophobic portion of this lipid is far longer than the fatty acid tails on membrane phospholipids! Possibly in a helical or folded conformation!