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1、DOI10.1515/hsz-2013-0282??Biol.Chem.2014;395(6):657–665AndréPaul,AnnaTrincone,SandraSiewert,GeorgHerrlerandChristelSchwegmann-We?els*Alysine-methionineexchangeinacoronavirussurfaceproteintransformsaretentionmotifintoanendocytosissignalAbstract:Transmissiblegastroenteritisvirus(TGEV)isanseve
2、reinnewbornanimals.Mortalityintheseanimalsenveloped(+)RNAvirusbelongingtothefamilyCorona-canreach100%(EnjuanesandvanderZeijst,1995).Threeviridae.Amongtheviralmembraneproteins,thespikemembraneproteinshavebeendescribedforTGEV:the(S)proteinmediatesreceptorrecognition/attachmentmembraneprotein(
3、M),thesmallmembraneprotein(E)tothehostcellandfusionofviralandcellularmem-andthespikeprotein(S).TheEproteinisrequiredforbranes.ThecytoplasmictailoftheSproteincontainsavirusmorphogenesisandmaturation(Fischeret?al.,1998;tyrosine-dependentsortingsignalwiththeconsensusOrtegoet?al.,2007).TheMprot
4、einplaysanimportantrolesequenceYXXΦ.InthecontextoftheSproteinofTGEVduringvirusassemblyandinteractswiththeE,S,and(1440YEPI1443),thismotifactsasaretentionsignal,pre-nucleocapsidproteins(Opsteltenet?al.,1995;Vennemaventingsurfaceexpressionoftheprotein.Here,weshowet?al.,1996;Narayananet?al.,200
5、0;Escorset?al.,2001).thatachimericSprotein,containingthesixC-terminalTheSproteinisthemajorinducerofvirus-neutralizingaminoacidsoftheglycoproteinGofvesicularstomatitisantibodiesandiscrucialforvirusentry(Godetet?al.,virus(VSV)isnolongerretainedintracellularly,despite1991,1994).Itmediatesvirus
6、attachmentbyinteractingthepresenceofthetyrosinetetrapeptidemotif.FollowingwithporcineaminopeptidaseN,thecellularreceptortransporttothecellsurface,thechimericproteinwasrap-proteinforTGEV,andfusionoftheviralmembranewithidlyendocytosed.Analysisofmutantproteinsgeneratedthehostcellmembrane(Delma
7、set?al.,1992;Gallagherbysite-directedmutagenesisrevealedthatasingleaminoandBuchmeier,2001;Schwegmann-Wesselset?al.,2002,acidexchange(1445K/M,position:+2downstreamofthe2011).Thebuddingeventduringthecoronavirusrepli-tyrosine-basedmotif)wasresponsibleforthe