分子医学 蛋白质修饰.ppt

ProteinModification

蛋白质修饰

Posttranscriptionalmodificationsofinsulin2

Posttranscriptionalmodificationsincluding:RemovalofN-MetDisulfidebondformationProteolyticprocessingChemicalmodifications: Phosphorylation(磷酸化) Acetylation(乙酰化) Methylation(甲基化) Ubiquitination(泛素化) SUMOylation(smallubiquitin-relatedmodifier) Glycosylation(糖基化) Myristylation(十四烷基化)andFarnesylation(法尼基化) ……Formoreinformation,see/wiki/Posttranslational_modification3

PTM:fourcategoriesCellResearch(2014)24:143–1604

Formoreinformation,see/wiki/Posttranslational_modificationRegulationofactivityturnactivityonturnactivityoffgenerateadifferentfunctionProtein-proteininteractionmodificationsitemaybeabindinginterfaceSubcellularlocalizationmodificationsitemaybeatargetingsignalmodificationmaybeamembraneanchorDegradationidentifytheproteinfordegradation……Whyareproteinsmodified?5

Proteinsneedtobeproperlymodified6

Methodstodetectproteinmodifications1Dor2DgelelectrophoresisWesternblot:needspecificantibodyEasternblot:usingprobestodetectlipids,carbohydrate,phosphorylationoranyotherproteinmodificationChIP:ChIP-on-chip;ChIP-SeqMS(massspectrometry)Bioinformatics……7

PhosphorylationchangesPIoftheprotein,whichcanbeeasilydetectedon2DgelsMSanalysisofC/EBPβafterinvitrophosphorylationbyMAPKand/orGSK3βProcNatlAcadSciUSA.2005,102(28):9766-71WesternblottingofErkDetectionMethods:examples8

Histonechiefproteincomponentsofchromatin H1,H2A,H2B,H3,H4,andH5posttranslationalmodifications:altertheirinteractionwithDNAandnuclearproteins. H3H4:longtails;canbemodifiedatseveralplaces,includingmethylation,acetylation,phosphorylation,ubiquitination,sumoylation,citrullinationandADP-ribosylation. ThecoreofthehistonesH2AandH2Bcanalsobemodified.HistoneCode:hypothesizedtobeacodeconsistingofcovalenthistonetailmodifications →epigenet