多肽设计原理和方法_精品文档.ppt

多肽设计原理和方法_精品文档.ppt

《多肽设计原理和方法_精品文档.ppt》由会员分享，可在线阅读，更多相关《多肽设计原理和方法_精品文档.ppt（20页珍藏版）》请在冰豆网上搜索。

多肽设计原则和多肽设计原则和方法方法多肽抗原的特点多肽抗原的特点l含有的epitope数目少；l抗原性比融合蛋白弱；l产生的抗原特异性通常比融合蛋白强；l是一种半抗原，需要连接载体蛋白；多肽设计的原则多肽设计的原则lHydrophilicity,tobesuretheantigenisonthesurfaceoftheprotein.lAntigenicity,aminoacidprovidesgoodbonds.lN-orC-terminalpeptide,fortheyareexposedinmostproteins.lContainsMHCIIpreferredmotifs.SuchasD,Y,P,andFwhoappearsinMHCmoleculesmostfrequently.lNohomologywithotherproteinsbyblast.lPreferthecytoplasmicdomainforatransmembraneprotein,fortheyaremoreimmunogeniclAvoidglycosylationandphosphorylationsitesifpossiblelAvoidcystininthemiddlepartofthepeptide20种氨基酸的抗原性比较种氨基酸的抗原性比较L0.75K-0.05H0.65P-0.05D0.31R-0.07T0.21W-0.11A0.12C-0.12E0.06N-0.14Y0.01G-0.18V-0.01M-0.38S-0.01F-0.77Q-0.03I-2.92什么时候选用多肽做抗原什么时候选用多肽做抗原l我们没有基因的抗原；l有基因，但是蛋白质和其他蛋白质有较强的同源性，或者蛋白质属于同源性较强的蛋白家族；l有基因，需要区分该基因编码的蛋白质加工后的不同亚型；l抗原是修饰蛋白质，包括磷酸化，乙酰基化蛋白质等案例案例1我们没有的蛋白质我们没有的蛋白质lNM_004445，EPHB6lMATEGAAQLGNRVAGMVCSLWVLLLVSSVLALEEVLLDTTGETSEIGWLTYPPGGWDEVSVLDDQRRLTRTFEACHVAGAPPGTGQDNWLQTHFVERRGAQRAHIRLHFSVRACSSLGVSGGTCRETFTLYYRQAEEPDSPDSVSSWHLKRWTKVDTIAADESFPSSSSSSSSSSSAAWAVGPHGAGQRAGLQLNVKERSFGPLTQRGFYVAFQDTGACLALVAVRLFSYTCPAVLRSFASFPETQASGAGGASLVAAVGTCVAHAEPEEDGVGGQAGGSPPRLHCNGEGKWMVAVGGCRCQPGYQPARGDKACQACPRGLYKSSAGNAPCSPCPARSHAPNPAAPVCPCLEGFYRASSDPPEAPCTGPPSAPQELWFEVQGSALMLHWRLPRELGGRGDLLFNVVCKECEGRQEPASGGGGTCHRCRDEVHFDPRQRGLTESRVLVGGLRAHVPYILEVQAVNGVSELSPDPPQAAAINVSTSHEVPSAVPVVHQVSRASNSITVSWPQPDQTNGNILDYQLRYYDQAEDESHSFTLTSETNTATVTQLSPGHIYGFQVRARTAAGHGPYGGKVYFQTLPQGELSSQLPERLSLVIGSILGALAFLLLAAITVLAVVFQRKRRGTGYTEQLQQYSSPGLGVKYYIDPSTYEDPCQAIRELAREVDPAYIKIEEVIGTGSFGEVRQGRLQPRGRREQTVAIQALWAGGAESLQMTFLGRAAVLGQFQHPNILRLEGVVTKSRPLMVLTEFMELGPLDSFLRQREGQFSSLQLVAMQRGVAAAMQYLSSFAFVHRSLSAHSVLVNSHLVCKVARLGHSPQGPSCLLRWAAPEVIAHGKHTTSSDVWSFGILMWEVMSYGERPYWDMSEQEVLNAIEQEFRLPPPPGCPPGLHLLMLDTWQKDRARRPHFDQLVAAFDKMIRKPDTLQAGGDPGERPSQALLTPVALDFPCLDSPQAWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQQHLRQQGSVEVl共1021aa，N-15aa为信号肽案例案例1我们没有的蛋白质（我们没有的蛋白质

（2）lWDEVSVLDDQRRLTRTFEAC案例案例1我们没有的蛋白质（我们没有的蛋白质（3）lGENEID:

2051EPHB6|EPHreceptorB6HomosapienslQuery1WDEVSVLDDQRRLTRTFEAC20lWDEVSVLDDQRRLTRTFEAClSbjct41WDEVSVLDDQRRLTRTFEAC60lGENEID:

814CAMK4|calcium/calmodulin-dependentproteinkinaseIVlQuery1lWDEVS-VLDDQRRLTRTFEA19lWDEVSVLD+RLTTF+ASbjct69WDEVSLNAKDLVRKLIVLDPKKRLT-TFQA97案例案例2家族性蛋白的多肽设计家族性蛋白的多肽设计（transgelin）lThetransgelinfamilyisagroupofproteinsthatbelongto22kdactin-relatedcorpninsuperfamily.lOfallthreeisoforms,transgelin1isthebestcharacterized.Transgelin1,alsoknownasSM22alpha,isaspecificmarkerfordifferentiatedsmoothmusclecells.lTransgelin2,alsoknownasSM22beta,isexpressedbybothsmoothmuscleandnon-smoothmusclecellsinatemporallyandspatiallyregulatedpattern.lTrangenlin3,alsoknownasNP25,isonlyfoundinhighlydifferentiatedneuronalcells.案例案例2家族性蛋白的多肽设计家族性蛋白的多肽设计（transgelin）2案例案例2家族性蛋白的多肽设计家族性蛋白的多肽设计（transgelin）3lTransgelin1:

KYDEELEERLVEWIIVQClTransgelin2:

QPGRENFQNWLKDGTVLC案例案例3家族性蛋白的多肽设计家族性蛋白的多肽设计RAB3A,3B,3ClSequence2:

NM_002866,RAB3A,memberRASoncogenefamilylSequence3:

NM_002867,RAB3B,memberRASoncogenefamilylSequence4:

NM_138453,RAB3C,memberRASoncogenefamily案例案例4家族性蛋白的多肽设计家族性蛋白的多肽设计actin对应的处理方法？

对应的处理方法？

案例案例5同一蛋白质不同亚型的多肽设计同一蛋白质不同亚型的多肽设计NFKB1lNFKB1,lNUCLEARFACTORKAPPA-B,SUBUNIT1;NFKB1lAlternativetitles;symbolslTRANSCRIPTIONFACTORNFKB1NUCLEARFACTOROFKAPPALIGHTCHAINGENEENHANCERINBCELLS1NFKBp105,INCLUDEDNFKBp50,INCLUDED案例案例5同一蛋白质不同亚型的多肽设计同一蛋白质不同亚型的多肽设计NFKB1lThisgeneencodesa105kDproteinwhichcanundergocotranslationalprocessingbythe26Sproteasometoproducea50kDprotein.The105kDproteinisaRelprotein-specifictranscriptioninhibitorandthe50kDproteinisaDNAbindingsubunitoftheNF-kappa-B（NFKB）proteincomplex.l1433aminoacidsoffulllength968p105proteinformp50.案例案例5同一蛋白质不同亚型的多肽设同一蛋白质不同亚型的多肽设计计NFKB1lMAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTADGPYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQAEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITFHPGTTKSNAGMKHGTMDTESKKDPEGCDKSDDKNTVNLFGKVIETTEQDQEPSEATVGNGEVTLTYATGTKEESAGVQDNLFLEKAMQLAKRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHSQLVRDLLEVTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAALLLDHPNGDGLNAIHLAMMSNSLPCLLLLVAAGADVNAQEQKSGRTALHLAVEHDNISLAGCLLLEGDAHVDSTTYDGTTPLHIAAGRGSTRLAALLKAAGADPLVENFEPLYDLDDSWENAGEDEGVVPGTTPLDMATSWQVFDILNGKPYEPEFTSDDLLAQGDMKQLAEDVKLQLYKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQAASSPVKTTSQAHSLPLSPASTRQQIDELRDSDSVCDSGVETSFRKLSFTESLTSGASLLTLNKMPHDYGQEGPLEGKI案例案例5同一蛋白质不同亚型的多肽设同一蛋白质不同亚型的多肽设计计NFKB1案例案例6同一蛋白质不同亚型的多肽设计同一蛋白质不同亚型的多肽设计CXCR3lTheCXCR3proteinbelongstoGprotein-coupledreceptorfamily.Severalalternativelysplicedtranscriptvariantsencodingdistinctisoformshavebeenreported.TheCXCR3Bproteincontains416aminoacidsandhasalongerNterminusthatdiffersfromtheoriginal368-aminoacidCXCR3protein,CXCR