《冠狀病毒Coronavirusl論文-2013 Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26.pdf》由會(huì)員上傳分享，免費(fèi)在線閱讀，更多相關(guān)內(nèi)容在學(xué)術(shù)論文-天天文庫。

1、LETTERdoi:10.1038/nature12328MolecularbasisofbindingbetweennovelhumancoronavirusMERS-CoVanditsreceptorCD2612113,411,511,6GuangwenLu*,YaweiHu*,QihuiWang*,JianxunQi*,FengGao*,YanLi,YanfangZhang,WeiZhang,YuanYuan,42711,5,6,7,8JinkuBao,BuchangZhang,YiShi,JinghuaYan&GeorgeF.

2、Gao13–15ThenewlyemergentMiddleEastrespiratorysyndromecoronavirusviruses,shouldmediatemembranefusion.Theexploitationofthe1,2(MERS-CoV)cancauseseverepulmonarydiseaseinhumans,repre-virus–receptorinteractionandthusoftheinterventionstrategiessentingthesecondexampleofahighlyp

3、athogeniccoronavirus,therequiresanatomicdelineationofthereceptor-bindingpropertiesof3firstbeingSARS-CoV.CD26(alsoknownasdipeptidylpeptidaseS1.Onthebasisofpreviousstudies,thereceptorattachmentsitesof4,DPP4)wasrecentlyidentifiedasthecellularreceptorforMERS-coronavirusS1su

4、bunitsmightlocatetoeithertheamino-terminal416CoV.TheengagementoftheMERS-CoVspikeproteinwithCD26(suchasinmurinehepatitisvirus)orthecarboxy-terminal(suchas17mediatesviralattachmenttohostcellsandvirus–cellfusion,therebyin,forexample,SARS-CoVandhumancoronavirusNL63(ref.18))

5、initiatinginfection.Herewedelineatethemolecularbasisofthisdomain.WethereforetestedindividuallythebindingofMERS-CoVS1specificinteractionbypresentingthefirstcrystalstructuresofbothanditsN-andC-terminal-domainproteinstocell-surface-expressedthefreereceptorbindingdomain(RBD

6、)oftheMERS-CoVspikeCD26molecules.Thereceptor-bindingcapacitywasattributedtotheproteinanditscomplexwithCD26.Furthermore,bindingbetweenC-terminalaminoacids367–606ofMERS-CoVS1(Fig.1b).WeherebytheRBDandCD26ismeasuredusingreal-timesurfaceplasmonreferredtothisdomainasRBD.Thep

7、otentinteractionbetweenMERS-resonancewithadissociationconstantof16.7nM.TheviralRBDCoVRBDandCD26wasfurtherdemonstratedbysurfaceplasmoniscomposedofacoresubdomainhomologoustothatoftheSARS-resonanceassays,inwhichCD26bindstoMERS-CoVRBDwitha52121CoVspikeprotein,andauniquestra

8、nd-dominatedexternalreceptordissociationconstant(Kd)ofabout16.7nM(Kon,1.79310Ms;2321bindingmotifthatrecognizes