资源描述：
《Chondroitin sulfate proteoglycan 4 functions as the cellular receptor》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、CellResearch(2015)25:157-168.npg©2015IBCB,SIBS,CASAllrightsreserved1001-0602/15ORIGINALARTICLEwww.nature.com/crChondroitinsulfateproteoglycan4functionsasthecellularreceptorforClostridiumdifficiletoxinB1111111PengfeiYuan,HongminZhang,ChangzuCai,ShiyouZhu,Yuex
2、inZhou,XiaozhouYang,RuinaHe,1123331ChanLi,ShengjieGuo,ShanLi,TuxiongHuang,GregorioPerez-Cordon,HanpingFeng,WenshengWei1BiodynamicOpticalImagingCenter(BIOPIC),StateKeyLaboratoryofProteinandPlantGeneResearch,SchoolofLifeScienc-2es,PekingUniversity,Beijing10087
3、1,China;SchoolofBioscienceandBiotechnology,SouthChinaUniversityofTechnology,3Guangzhou,Guangdong510006,China;DepartmentofMicrobialPathogenesis,UniversityofMarylandDentalSchool,Balti-more,Maryland21201,USAAsagram-positive,spore-forminganaerobicbacillus,Clostr
4、idiumdifficile(C.difficile)isresponsibleforsevereandfatalpseudomembranouscolitis,andposesthemosturgentantibioticresistancethreatworldwide.EpidemicC.difficileistheleadingcauseofantibiotic-associateddiarrhoeaglobally,especiallydiarrhoeaduetotheemergenceofhyper
5、virulentstrainsassociatedwithhighmortalityandmorbidity.TcdB,oneofthekeyvirulencefactorssecret-edbythisbacterium,entershostcellsthroughapoorlyunderstoodmechanismtoelicititspathogeniceffect.HerewereportthefirstidentificationoftheTcdBcellularreceptor,chondroiti
6、nsulfateproteoglycan4(CSPG4).CSPG4wasinitiallyisolatedfromawhole-genomehumanshRNAmirlibraryscreening,anditsrolewasconfirmedbybothTALEN-andCRISPR/Cas9-mediatedgeneknockoutinhumancells.CSPG4iscriticalforTcdBbindingtothecellsurface,inducingcytoskeletondisruptio
7、nandcelldeath.AdirectinteractionbetweentheN-terminusofCSPG4andtheC-terminusofTcdBwasconfirmed,andthesolublepeptideofthetoxin-bindingdomainofCSPG4couldpro-tectcellsfromtheactionofTcdB.Notably,thecompletelossofCSPG4/NG2decreasedTcdB-triggeredinterleukin-8induc
8、tioninmicewithoutsignificantlyaffectinganimalmortality.Basedonboththeinvitroandinvivostudies,weproposeadual-receptormodelforTcdBendocytosis.ThediscoveryofthefirstTcdBreceptorrevealsapreviouslyun
