Oglycosylation(o糖基化)重点.pptx

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Oglycosylation(o糖基化)重点.pptx

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IntroductiontoGLYCOBIOLOGYMar–Jun,2013Chapter5O-linkedGlycosylationMucin-typeO-glycans(O-GalNAc)O-glycansinproteoglycan(O-Xyl,O-GalNAc)O-FucO-GlcNAc……PlaystructuralorsignalrolesMucin:黏蛋白;Proteoglycan:蛋白聚糖Hyl：4-hydroxylysineLinkageofMucin-typeO-GlycanstoProteins5.1Mucinsarelarge,heavilyO-glycosylatedproteinsholdingwaterFunction:Theprimarypurposeofmanymucinsistoretainwater.Distribution:Mucinspresentatthesurfacesofthedigestiveandgenitaltractsandintherespiratorysystem.Mucinsindifferentorgansarecharacterizedbydifferentpolypeptidebackbonestructurestowhichthesugarsareattached.Mechanism:Additionofclustersofsialylatedglycanstogroupsofserineandthreonineresiduesresultsinregionsofstrongnegativechargethatgivethemucinsthecapacitytobindlargeamountsofwater.Twoportions:sugarandpolypeptidesMucin-typeO-glycanswithcore1andcore2structuresTantigenMucinGlycansMucinPolypeptidesAtleast19humanmucingeneshavebeendistinguishedbycDNAcloning.Mucinpolypeptides:long,asmanyas10,000aminoacids,polymorphicTandemrepeat(串联重复):富含Ser和Thr,序列具蛋白和种属特异性,长10-80aa，在肽链分子中可多达百余拷贝Uniquesequences:specifyingsecretion,membraneinsertion,oligomerization,andbacterialbindingfunctions;furtherO-andN-glycosylated.Theamino-andcarboxy-terminalregionsareverylightlyglycosylated,butrichincysteines.Thecysteineresiduesparticipateinestablishingdisulfidelinkageswithinandamongmucinmonomers.SchematicofIntestinalSecretoryMucin(MUC2)GalNAcGalSiavonWillebrandfactorCdomainsvonWillebrand:冯-威尔布兰德vonWillebrandfactorDdomains1-10MDa寡糖体积Sia电荷排斥延伸构型黏弹润滑Inadditiontoaidinginwaterretention,themucinsserveaslubricationandalsohelptoprotectfrominvasionbymicro-organismsHowtoprotect:Entrappotentialpathogens;Someterminaldomainshaveaspecificaffinityforbacterialcellsurfaces,whichcanenhanceentrapmentandmayalsoleadtoimmuneresponsesagainsttheboundorganismsInadditiontoprovidingfunctionssimilartothoseofthesecretedmucins,thecellsurfacemucinscanregulateadhesionbetweencells.MUC1ASGP1/2MUC1:膜黏蛋白ASGP:ascitessialoglycoprotein(腹水唾液酸糖蛋白)球形域2球形域1CellSurfaceMucin(MUC1)wit