growth factor rattled out of its cage 2017 taekjip ha学术.pdf

该【growth factor rattled out of its cage 2017 taekjip ha学术 】是由【探春文档】上传分享，文档一共【2】页，该文档可以免费在线阅读，需要了解更多关于【growth factor rattled out of its cage 2017 taekjip ha学术 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。NEWS&VIEWSdoi:-domainthroughintegrins,whicharepresumablypower-edbyactin-filamentmove-ments(Fig.?1).Thisactionloosensthepro-domainandreleasestheactivegrowthfactorGrowthfactorrattledforlocaluse(ortomakeitavailabletonearbycells).Inasense,TGF-esinabox,giftwrappedwithribbons—-?1islocatedinsideaproteincage,andisthoughttobeTounderstandthisprocessbetter,-?-raycrystallographytodeterminecomplexwithintegrinαV?--domain,althoughnotitscontents,-,ofwhichaVb6activatesInterestingly,biophysicalmeasurementsuchlikehumans,cellsoftenexchangetheproteinTGF--CagedTGF-b1islinkedtotheextracellularbindingaffinitybetweenTGF-b1andtheforminggrowthfactor-b(TGF-b)matrixthroughanadaptorprotein,andcon-pro-domainisnotaffectedbyintegrinbind-MfamilyactaskeychemicalsignalsforsuchsistsofalatentversionoftheTGF-,then,-terminalchange?theyarepackagedinsideaproteincage,and‘pro-domain’thathasbeencleavedawayfromDongandcolleaguesnotedthatthebindingessedbycellsonlywhenthecagetheproteinproper—thisregionstablywrapsinterfacebetweenthepro-,prevent-highlyinterdigitated,?—differentfromtheflatcontactsfoundmembraneproteinscalledintegrinsarerespon-TGF-b1throughinteractionswithasequenceatmostprotein–-bproteinsoutoftheirofthreeamino-acidresidues(arginine,glycine,,Donget?;RGD)onthepro-–RGDbindingisessentialforTGF-b1pre-existingstructuresofcagedTGF-b1andaTGF-bcage,andshowwithunprecedentedsignalling:mutationofasingleRGDresidueinintegrins(-pletedeletionofTGF-b1,includingmulti-tion)oranalysesofpreviousstructuresofinte-(whichrevealedextracellularmatrix,whichsurroundstheoftheblood-).However,thiscell,tothecytoskeleton,whichconsistsofAnattractivemodelhasemergedininterdigitationandtheassociatedlargebind-filamentsofactinproteinandprovideswhichacellthatneedsTGF-b1yanksontheinginterfaceareprobablyresponsiblefortheabcActinForceonactinTGFβRCytoplasmCellexteriorInterfaceIntegrinαvIntegrinβ6Pro-domaincageTGF-β1AdaptorExtracellularmatrixFigure1|Force-inducedactivationofTGF-β1.?a,?Initslatentform,thewithactin--factorproteinTGF-b1issurroundedbyanextensiontoitsb,?TheauthorsfindthatbindingofTGF-b1totheintegrinsubunitsleadsamino-terminalregionknownasapro-domain,-,,,?Thecageopens,Donget?-b1boundtoacell-membranereleasingactivatedTGF-,whichmakescontactprotein,TGFbR.?2017MacmillanPublishersLimited,.|NATURE|1RESEARCHNEWS&VIEWSstableorientationbetweenintegrinandcagedofforce-inducedTGF-b1activationisusingfluorescence--b1,,resolutioncouldbeachievedforTGF-bactiva-asecondtechniqueforstructuredetermina-unlikeTGF-b1andTGF-b3,thepro-domaintion,itwouldallowresearcherstodeterminetion,small-angleX--ofTGF-b2lacksarecognizableintegrinbind-whetherthereleasedgrowthfactorsareusedresolutiontechniquedoesnotsufferfromtheingmotifsuchasRGD(ref.?1).Themechanismbythecellsthatdotheuncagingorbythesur-potentialforartefactscausedbycrystalpack-bywhichTGF-,,Dongandcolleagues’-Theimportanceofastablebindingorienta-TGF-?-workers’veryhighforcesintheirsimulations,---difficultquestionsaboutthelinksbetweenappliedtothepro-domainthroughb6integrin,subtlechangestothepro-municationthecageopened,.■,applyingWouldaVb6remainboundtothepro-domaintheforcethroughaVcausedthissubunittoattheseforces,asitdidinthesimulations,orTaekjipHaisintheDepartmentsofunfoldbeforeanymajorstructuralchangestoisthebindingseeninthesimulationsanarte-Biophysics,BiomedicalEngineeringandthepro--factoftheextremeforcesused?AnsweringthisBiophysicsandBiochemistry,JohnsHopkinsgestthatforceapplicationinthecorrectori-questionwillprovideakeytestofthecurrentUniversity,HowardHughesMedicalInstitute,entation—thatis,throughtheregionofthemodel,becausetheunbindingforcebetweenBaltimore,Maryland21205,-domainthatcontactsb6—isessentialfortheintegrinandthepro-domainshouldbease-mail:******@,.&Rifkin,,single-,355–372(2013).,://dx./,allsub-domainsinb?integrinsarecon-forcesacrossintegrinsduringunbindingandnature21035(2016).nectedtoadjacentsubdomainsbytwocova-uncaging7,-Moruno,,7048–7067(2016).lentbonds,whereasina?,,319–328(1999).-,,787–793(2007).thatforceissecurelytransmittedthroughreleasedgrowthfactor,andassuchisindirect,,,343–349(2011).b?integrins,andthata?,F.,Garcia,.,Mould,.,Humphries,.&Zhu,,1275–1284(2009).-bsandintegrinsarosecontrast,theroleofintegrinsinanotherpro-,X.&Ha,,991–994(2013).duringthesameevolutionaryperiodandincess(remodellingextracellularmatrices),,1075–1090icbranch,themechanismbedirectlyexaminedatsingle-cellresolution(2000).2|NATURE|?2017MacmillanPublishersLimited,.