高级微生物2014

一、细胞通讯(cellcommunication)与信号转导(signaltransduction)概述二、双组分调控系统（Two-componentregulatorysystem）三、CyclicNucleotideSecondMessengersinBacteria四、群体感应（Quorum-Sensing）,微生物细胞通讯和信号转导,一、细胞通讯(cellcommunication)与信号转导(signaltransduction)概述细胞通讯是细胞间或细胞内通过高度精确和高效地发送与接收信息的通讯机制，对环境作出综合反应的细胞行为。,细胞信号转导细胞通过位于胞膜或胞内的受体感受胞外信息分子的刺激，经复杂的细胞内信号转导系统的转换来影响细胞的生物学功能。,Whatispopularinresearchtoday？信号转导（细胞周期调控；细胞凋亡；细胞衰老；DNA损伤与修复）美国科学情报研究所根据SCI收录及引用论文检索，全世界自然科学研究中论文发表最集中的三个领域分别细胞信号转导,细胞凋亡,基因组与蛋白组学研究细胞信号转导研究的3部分接收信号的特定受体受体后的信号转导通路信号的生物学效应,细胞通讯的一般过程,信号分子的产生信号分子细胞识别（Cellrecognition）受体蛋白信号转导（Signaltransduction）胞内信号特定基因表达应答反应,细胞将胞外信号(分子A)转变成胞内的信号(分子B),电话接收器将电信号转换成声信号,细胞通讯与信号传递引起的反应,酶活性的变化基因表达的变化细胞骨架构型通透性的变化DNA合成活性的变化细胞死亡程序变化等。,细胞通讯的作用,细胞间的通讯对于多细胞生物体的发生和组织的构建，协调细胞的功能，控制细胞的生长、分裂、分化和死亡是必须的。,CELLCOMMUNICATION,SectionA:AnOverviewofCellSignaling,1.Cellsignalingevolvedearlyinthehistoryoflife2.Communicatingcellsmaybeclosetogetherorfarapart3.Thethreestagesofcellsignalingarereception,transduction,andresponse,Cell-to-cellcommunicationisabsolutelyessentialformulticellularorganisms.Cellsmustcommunicatetocoordinatetheiractivities.Communicationbetweencellsisalsoimportantformanyunicellularorganisms.Biologistshavediscoveredsomeuniversalmechanismsofcellularregulation,involvingthesamesmallsetofcell-signalingmechanisms.Cellsmayreceiveavarietyofsignals:chemicalsignals,electromagneticsignals,andmechanicalsignals.,Introduction,Onetopicofcell“conversation”issex.TheyeastSaccharomycescerevisiae,theyeastofbread,wine,andbeer,identifiesitsmatesbychemicalsignaling.Therearetwosexes,aandalpha,eachofwhichsecretesaspecificsignalingmolecule,afactorandalphafactorrespectively.Thesefactorseachbindtoreceptorproteinsontheothermatingtype.,1.Cellsignalingevolvedearlyinthehistoryoflife,Oncethematingfactorshaveboundtothereceptors,thetwocellsgrowtowardeachotherandexperienceothercellularchanges.Twooppositecellsfuse,ormate.Thea/alphacellcontainsthegenesofbothcells.,Theprocessbywhichasignalonacellssurfaceisconvertedintoaspecificcellularresponseisaseveralstepsinasignal-transductionpathway.Themoleculardetailsinbothyeastandanimalcellsarestrikinglysimilar,eventhoughtheirlastcommonancestorwasoverabillionyearsago.Signalingmoleculesevolvedfirstinancientprokaryotesandwerethenadoptedfornewusesbysingle-celledeukaryotesandmulticellulardescendents.,Cellsignalinghasremainedimportantinthemicrobialworld.Myxobacteria,soil-dwellingbacteria,usechemicalsignalstocommunicatenutrientavailability.Whenfoodisscarce,cellssecreteasignaltoothercellsleadingthemtoaggregateandformthick-walledspores.,Fig.11.2,Individualrod-shapedcells,Spore-formingstructure(fruitingbody),Aggregationinprocess,Fruitingbodies,0.5mm,1,3,2,AplasmamembraneisessentialforacellItdoesisolatethecellfromitssurroundingsAcellcannotsurviveifitcannotsensechangesintheextracellularenvironmentandrespondtothem,CellcommunicationistheprocessofcellsdetectingandrespondingtosignalsintheextracellularenvironmentNeededtocoordinatecellularactivitiesinamulticellularorganismOneimportantreasonforcellcommunicationistopromotecelldivision,CellcommunicationorcellsignalinginvolvesincomingandoutgoingsignalsSignalsareagentsthatinfluencethepropertiesofcellsSignalsaffecttheconformationofareceptorleadingtoaresponseinthecell,Whydocellsneedtorespondtosignals?,NeedtorespondtoachangingenvironmentAdaptationoracellularresponseiscriticalforsurvivalGlucoseactsasasignaltoyeastcellstoincreasenumberofglucosetransportersandenzymesallowingefficientuptakeanduseofglucose,Signal-TransductionEmphasis,Thischaptersemphasisisonsignalsthatarereleasedfromonecellandallowedtofreelydiffusetoasecond(ormore)recipientcell(s)Thesecommunicationsaredeliberatelyinitiated,received,andinterpretedinordertoincreasethephysiologicalcoordinationofthecellsinmulticellularorganismsWewillconsiderinparticularthoseeventsthatfollowthereceptionofchemicalsignals,ThreeStagesofSignalTransduction,ReceptionofextracellularsignalbycellTransductionofsignalfromoutsideofcelltoinsideofcelloftenmulti-steppedNotenotnecessarilytransductionofligandCellularResponseResponseisinititiatedand/oroccursentirelywithinreceivingcell,ThreeStagesofSignalTransduction,ThreeStages,2a.Transduction,2b.Transduction,2c.Transduction,2d.Transduction,ResponsesusuallyinvolveincreasingordecreasingsomeProteinsFunction,ThreeStages,2a.Transduction,2b.Transduction,1.Reception,3.Response,物理信号：光、热、电流化学信号：最广泛的信号是化学信号。短肽、蛋白质、气体分子（NO、CO）以及氨基酸、核苷酸、脂类和胆固醇衍生物等。信号分子的共同特点：特异性，只能与特定的受体结合；高效性，几个分子即可发生明显的生物学效应，这一特性有赖于细胞的信号逐级放大系统；可被灭活，完成信息传递后可被降解或修饰而失去活性，保证信息传递的完整性和细胞免于疲劳。,信号分子与靶细胞,一、信号分子与信号细胞,信号分子非营养物非能源物质非结构物质不是酶主要是用来在细胞间和细胞内传递信息,根据细胞受体蛋白组检测可用的特定信号组(数百种信号分子)细胞按细胞内的装置对接收的信息在细胞内进行不同的整合和译解,二、靶细胞,信号分子作用的效应细胞,专一识别信号,反应差异,细胞按发育编程，在不同的分化阶段，分别与不同的专一性信号分子结合,靶细胞中的受体,受体概念:能够识别和选择结合信号分子并能引起一系列生物学效应的生物大分子.多为糖蛋白,信号分子可直接穿越质膜脂双层进入靶细胞内部，与细胞内受体结合，激活受体，同专一DNA序列结合，调控基因表达！,1、胞内受体:,于细胞质溶质或核中,在30min内直接诱导少数专一基因转录,初级反应的转录产物又激活其它基因,一些疏水性信号小分子的受体,亲水性信号分子的受体,2、表面受体,同信号配体结合后，将细胞外信号转变成细胞内信号，引起靶细胞的反应,离子通道偶联受体(ion-channel-linkedreceptors),G-蛋白偶联受体(G-protein-linkedreceptors),间接调节结合在质膜上靶蛋白(酶或离子通道)的活性,G-蛋白(trimericGTP-bindingregulatoryprotein),酶偶联受体(enzyme-linkedreceptors),一次穿膜的蛋白质，外端有配体结合部位，内端为催化部位,多为蛋白质激酶或与蛋白质激酶结合在一起，被激活后，可使靶细胞中专一的蛋白质发生磷酸化,多次穿膜蛋白，信号传递由少量神经递质介导,递质门离子通道(transmitter-gatedionchannels),信号转换器(signaltransducer),细胞表面与细胞内受体:,表面受体(surfacereceptor)细胞质膜上：主要是同大的信号分子或小的亲水性的信号分子作用细胞内受体(intracellularreceptor)胞质溶胶、核基质中：同脂溶性的小信号分子作用,一、胞内信号传递的级联反应,一个哺乳动物细胞：约含有100余种蛋白质激酶，人类基因组中有1的基因为蛋白质激酶编码!,信号分子受体,细胞反应,细胞反应,细胞内信号传递的基本原理,二、细胞对细胞外信号反应的不同速率,激素G蛋白偶联受体G蛋白腺苷酸环化酶cAMPA激酶基因调节蛋白磷酸化激活特定基因表达,1、快速反应：,2、慢速反应：,激活Ser/Thr激酶胞内某些蛋白Ser或Thr磷酸化改变细胞行为,要涉及到对基因表达的调节,第二信使的概念(secondmessenger),大多数激素类信号分子不能直接进入细胞，只能通过同膜受体结合后进行信息转换，通常把细胞外的信号称为第一信使，而把细胞内最早产生的信号物质称为第二信使。,第二信使,第二信息至少有两个特征:是第一信息同其膜受体结合后最早在细胞膜内侧或胞浆中出现，仅在细胞内部起作用的信息分子；能启动或调节细胞内稍晚出现的反应。目前公认的第二信息有cAMP、DG、IP3、cGMP和Ca2+。,二、双组分调控系统（Two-componentregulatorysystem）,Lifeinthemicrobialworldisnopicnic,EnviromentalfluctucationsScarcityofNutritionCompetitorslurkingateveryturn,Strongselectivepressure,Howtosurvive,?,Therefore,Theremustbemechanismsbywhichbacteriareceivesignalsfromtheenvironmentandtransmitthemtothespecifictargettoberegulated.,1、Whatissignaltransduction,微生物必须对生存条件的变化迅速作出反应；必须与其它个体或群体进行竞争，获取并有效地利用营养物质。,必须能够产生、感应、传递信号，同时对多个相关的操纵子进行系统性调控。,Cellularresponse,Two-componentregulatorysystemSensorkinaseEnzyme-linkedreceptorHydrolyzesATPandphosphorylatesPhosphategrouptransferredtoresponseregulatorResponseregulatorRegulatesexpressionofmanygenes,Whereare2-ComponentSystemsFound?（2CS）,Bacteria(absentinparasiticbacteria)PlantsFungiSlimemoldsNote:Theyarenotfoundinmammals!,Thesignaltransductionmodulesviatransmembranereceptors,HisKin-histidinekinase(HK)ACyc-adenylatecyclaseSTYK-serine-threonine-tyrosinekinaseGGDEF,HD-GYP,EALMCP-Methyl-acceptingchemotaxisproteins,ASMNews71(2005):326-,Notallsensorsenseenvironmentalsignals,Almost1/3HKandcloseto1/2oftheACyc,DDGEF-,EAL-,STYKproteinsarenotmembraneboundThecytoplasmicsensordomainsaremodulatedbyintracellularsignals,Cellulartargets,STYKRegulatetheexpressionorfunctionofsigma,anti-sigma,andanti-anti-sigmafactorsHisKRR(responseregulator)TCSor2CS(twocomponentsystem)c-di-GMPAcycPseudomonasaeruginosaAcycregulatestheexpressionoftypeIIIsecretionsystemgenesMCPsflagellarmotorCCWorCWrotation,Bacterial2-ComponentSignalTransductionSystems,1.Component1:Sensorkinase,i)Substratereceptor,signalrecognitiondomain,inputdomain(periplasmic),ii)Signaltransductiondomain,membranespanningregion,iii)Autokinasedomain,phosphorylationdomain(cytoplasmic),a)ATPbinding(sub)domain,b)phosphorylation-phosphotransfer(sub)-domain,2.Component2:Responseregulator,i)Phosphorylationdomain,ii)DNAbindingdomain,Simplestcase:transcriptionalactivatorwhenphosphorylated,Firstcomponentistypically(auto)-phosphorylatedonaHisresidueandtransferstoaAspgroupontheresponseregulator(secondcomponent).,细胞信号转导（cellularsignaltransduction)细胞通过位于胞膜或胞内的受体感受胞外信息分子的刺激，经复杂的细胞内信号转导系统的转换来影响细胞的生物学功能。,双组分信号转导系统,双组分信号转导系统又名双组分磷酸接力系统，是一种通过磷酰基团的转移来转导信号，并控制基因转录的调节系统。双组分是：传感蛋白激酶、应答调节蛋白。双组分系统广泛存在于细菌中，也存在于真核微生物中；高等真核生物也利用磷酸化这一机制转导信号。,Two-componentsignaltransductionsystem(2CS/TCS),H,Signal,D,HTH,Inputdomain,Transmitterdomain,Receiverdomain,outputdomain,cytoplasm,innermembrane,Sensorkinase-HK,Responseregulator-RR,2CSphosphorelay,*N-transmembranedomainforsignalinginput*Transmitterdomain(conservedhistidineresidue)Bifunctionalaskinaseorphosphatase(unphosphorylatedform),*AconservedN-receiverdomain(Aspartateresidue)*AvariableC-terminaloutputdomain,Differenttypesofkinasedomain,MicroMolBiolRev(2006)Dec,Differenttypesofresponseregulators,AvariableC-terminaloutputdomainLackC-effectordomainCheYassociatedwithFliM(flagellarmotor)DNA-bindingdomainEnzymeCheB(chemotaxismethylesterase)RegA(cAMPphosphodiesterase)C-di-GMPcyclaseorphosphodiesterase,ResponseRegulator,N-terminalReceiverorRegulatorydomainC-terminalEffectordomain:DNA-bindingtranscriptionalregulatorenzymaticactivity(CheBorRegA)protein-proteininteractionsCatalyzethetransferofphosphrylgroupfromphospho-HKtoconservedasparticacid:phosphorylationresultsinconformationalchangeofresponseregulator.Manyalsocatalyzeauto-dephosphorylation.,Classicalsystem,Unorthodoxsystem,Hybridsystem,InputTransmitterReceiverHptReceiverOutput,NG1FG2,H,D,D,NG1FG2,H,D,D,NG1FG2,D,(Rodrigueetal.,2000),HTH,HTH,HTH,Phosphorelay,Obligatephosphorelay,His,Asp,His,ATP,ADP,P,P,P,Asp,P,BvgS,BvgA,Asp,P,EvgA,Asp,P,BvgA,Bordetellapertussis-(百日咳桿菌)BvgAS-acentralregulatorofvirulencegenes(pertussistoxingenesptxandthegenesforsecretionpts),E.coli2CSforvirulencegenesexpression,Optionalphosphorelay,His,Asp,His,ATP,ADP,P,P,P,Asp,P,ArcB,ArcA,Asp,P,Asp,P,OmpR,CheY,Asp,P,ArcA,ArcAB-responsetoanaerobicenvironment(control20genes),Two-componentsystem,Essentialsofphosphotransferreactions,Autophosphorylation:HK-His+ATPHK-HisP+ADPPhosphotransfer:HK-HisP+RR-AspHK-His+RR-AspPDephosphorylation:RR-AspP+H20RR-Asp+PiAlternativemechanisms1.HKPhosphatases:HK-HisP+PPHK-His+Pi2.RRPhosphatases:RR-AspP+PPRR-Asp+Pi,ProteinkinasescanbedividedintotwogroupsMembrane-associatedproteinsSenseenvironmentalsignalsCytoplasmicproteinsUsuallypartofapathwaythatismorecomplexthanasimpletwo-componentmechanismRespondtointracellularsignals,Histidinekinase,*Approximately250aminoacidsinlength*Containsseveralconservedsequencemotifs,Responseregulator,Minimumof120aaConservedspacingofhydrophobicresidues,HPt:His-containingphosphotransfer,Modificationofthe2-ComponentPathway:ThePhosphorelay,ModularOrganizationoftcs,E.coliosmoregulation,E.coliAnoxicRedoxRegulation,E.colichemotaxis,B.subtilissporulation,Twocomponentsystems,Early80sNtrB/NtrC-nitrogenassimilationEnvZ/OmpR-osmoregulationPhoR/PhoB-phosphatescavengingDctB/DctD-dicarboxylatetransportVirA/VirG-virulence,P.aeruginosa135个,SynechocystisPCC680382个,AnabaenaPCC7120211个,双组份系统基因,E.coli62个,Methanobacteriumthermoautotrophicum24个,蛋白激酶nNTPnNDP蛋白质蛋白质-nPinPiH2O蛋白磷酸酶,信号转导中的蛋白质可逆磷酸化,蛋白磷酸酶(proteinphosphatase，PP）蛋白磷酸酶的分类与蛋白激酶相对应，分为丝氨酸/苏氨酸型蛋白磷酸酶和酪氨酸型蛋白磷酸酶。有些酶具有双重底物特异性。对蛋白磷酸酶的研究还不如蛋白激酶那样深入。但两者的协同作用在细胞信号转导中的作用是不言而喻的。,ResponsesMediatedby2-ComponentSystems,BacteriaAdaptationtochangingosmolaritySporulationChemotaxisN2metabolismRedoxstatusofcellLightVirulenceandmanymore!,TwoComponentSystems,Regulate:nutrientacquisitionNitrogenPhosphateCarbon,TwoComponentSystems,Regulate:EnergymetabolismElectrontransportsystemsUptakemachineryCatabolicmachinery,TwoComponentSystems,Regulate:VirulencePlasmidtransferDegredativesecretionsToxinproductionAdherencefactorsIntracelleularsurvivalfactors,TwoComponentSystems,Regulate:AdaptationtophysicalorchemicalaspectsoftheenvironmentpHOsmolarityLightquality,TwoComponentSystems,Regulate:ComplexdevelopmentalpathwaysSporulationFruitingbodyformationSwarmercellproduction,蓝细菌中的双组份系统和功能,NarQ/NarL：Two-componentregulatorysystem,NarQ/NarLTwo-componentregulatorysystemSensespresenceofnitrate(NO3-)andnitrite(NO2-)BindingphosphorylatesNarQTransfersphosphatetoNarL(responseregulator)Activatesgenesinvolvedinnitrateandnitritemetabolismandtransport,在豆科植物根瘤中，类菌体只能利用四碳二羧酸作为其能量来源进行生物固氮,succinate,Lmalate,fumarate,aspartate,Oxalacetate,C4-dicarboxylicacids（DCA）,中华苜蓿根瘤菌四碳二羧酸运输（dct）系统,枯草杆菌调控芽孢形成的双组分系统,枯草杆菌调控芽孢形成的双组分磷酸接力系统,磷酸化的SpoOA能够激活F、E等Sigma因子的合成。当细胞内的部分A被F、E取代时，芽孢开始形成，负责芽孢形成后期基因的转录的G和K逐渐产生。,在营养生长阶段，枯草杆菌RNA聚合酶利用A对与其营养生长有关的基因进行转录；KinA、B、C、D等对环境信号进行传感反应的蛋白激酶，在营养细胞中以非磷酸化的形式存在。当这些激酶感应到不适于生长的信号时发生磷酸化；磷酸化的KinA等将磷酸基团转移到SpoOF；SpoOF将磷酸基团传递给SpoOB；SpoOB再将磷酸基团传递给SpoOA。磷酸化的SpoOA能与abrB基因的启动子结合并阻遏abrB基因的表达，AbrB是许多基因表达的抑制蛋白。,Chemotaxisofbacteria：2CS,MotilityofE.coli,E.colicanmovebyrotatinghelicalflagellarfilaments,Clockwise(CW)=tumble,Counter-clockwise(CCW)=run,Chemotaxisofbacteria,ChemotacticBehaviorofFreeSwimmingBacteria,chemotaxis:Directedmovementtowardsanattractantorawayfromrepellent,Components:,Signaltransductionproteins,Adaptationproteins,Receptorproteins,4、Themechanismofchemotaxis,Receptorproteins,=methyl-acceptingchemotaxisproteins(MCPs),Sensethepresenceofattractantsandrepellents.,Sensewhethertheconcentrationofthesubstanceincreasesordecreases,Tsr：Taxisserineandsomerepellents;Tar：TaxisaspartateandsomerepellentsTrg：TaxisriboseandgalactoseTap：Taxistodipeptides,InE.coli,fivedifferentchemoreceptorshavebeenidentified.Fourofthemareinvolvedintransmembranesignaling:,Signaltransductionproteins,CheA:sensorkinase;phosphorylatesitselfCheY:responseregulator;regulatethedirectionofrotationoftheflagellumCheW:universalcouplingproteinlinksthechemoreceptortotheCheACheZ:dephosphorylatesCheY-P,Adaptationproteins,CheR:methyltransferaseaddmethylgroupstoreceptorCheB:responseregulatorreceivephosphorylfromCheA-Pdemethylase,AdaptationPathway,MCPCheA(CheW),MCPCH3CheA(CheW),CheR,CheBP,Lessactive,Moreactive,CheA,CheA,CheW,CheW,+CH3,Flagellarmotor,Cytoplasmicmembrane,Cellwall,chemical,Transducer(MCP),CheR,TheMolecularMechanismofChemotaxis,Attractantsbindreceptorsatthecellsurfacechangingtheir“state”,TheMolecularMachineryofChemotaxis,TheactivetransducercausesachangeintheautophosphorylationofCheAtoformingCheA-P,CheA,CheA,CheW,CheW,+CH3,Flagellarmotor,Cytoplasmicmembrane,Cellwall,chemical,Transducer(MCP),CheR,p,TheMolecularMachineryofChemotaxis,CheAtransfersitsphosphatetoasignalingproteinCheYtoformCheYP.,CheA,CheA,CheW,CheW,CheY,CheY,+CH3,Flagellarmotor,Cytoplasmicmembrane,Cellwall,chemical,Transducer(MCP),CheR,P,CheY-Pinteractswiththeflagellarmotortoinduceclockwiseflagellarrotationandtumbling.,TheMolecularMachineryofChemotaxis,ThesignalisalsomodulatedbyCheZwhichdephosphorylatesCheY.,CheA,CheA,CheW,CheW,CheY,CheY,+CH3,Flagellarmotor,Cytoplasmicmembrane,Cellwall,chemical,Transducer(MCP),CheR,P,CheZ,Bindingattractant:CheAinhibited;CheYincreases;motorturnsCCW=smoothswimmingBindingrepellent:CheAactivated;CheY-Pincreases;motorturnsCW=tumble,TheMolecularMachineryofChemotaxis,Adaptationinvolvestwoproteins,CheRandCheB,whichallowsresettingofthesignalstateofreceptoreventhoughconcentrationofthechemicalremainsunchanged.,CheA,CheB,CheA,CheW,CheW,CheY,CheY,CheB,CheZ,+CH3,-CH3,Flagellarmotor,Cytoplasmicmembrane,Cellwall,chemical,Transducer(MCP),CheR,Adaptation,Ifthelevelofanattractantremainshigh:cheAremainlow;CheYandCheBlow;thecellswim;methylationofreceptorincrease;receptornolongerresponsetoattractant;P-CheAincrease;P-CheBincrease;celltumble;receptorcanbemethylated;responsetoattractantagain.,Chemotaxisandmotility,MCPstimulatesHKCheAautophosphorylationatHis-48relaysthephosphategrouptoRRCheY(atAsp-57)Phospho-CheYbindstotheflagellarmotortoinduceclockwise(CW)rotation,Thechemotaxispathway,PNAS(2008)105:6403-,CheAsensorkinase,AdaptorproteinCheW,CheZphosphatase,Methylesterase,Methyltransferase,MCP-CheBR,CheYresponseregulator,Motor,FRAP-fluorescencerecoveryafterphotobleaching,Agrobacterium/plantInteractionsSingaling,Agrobacterium/plantinteractions,opines,AgrobacteriuminatwoundsitetransfersT-DNAtoplantcell.,Agrobacteriuminsoiluseopinesasnutrients.,Acetosyringoneisproducedbywoundedplantcells(phenoliccompound).,Agrobacteriuminfectionsucceedsonlyonwoundedplants,OverviewoftheInfectionProcess,Agrobacteriumtumafacienssensesacetosyringoneviaa2-component-likesystem,3components:ChvE,VirA,ATP-binding,Note:ThevirA-virGsystemisrelatedtotheEnzZ-OmpRsystemthatrespondstoosmolarityinotherbacteria.,三、CyclicNucleotideSecondMessengersinBacteria,MicroReview:C-di-GMP:thedawningofanovelbacterialsignalingsystem,C-di-GMPisemergingasanovelglobalsecondmessenger.Recentfindingsshowinvolvementincellmetabolismandbiologicalprocessesinthecell.GGDEFdomainproteininvolvedinc-di-GMPsynthesis.EALdomainproteininvolvedinc-di-GMPdegradation.Thesetwoproteinsaffectcelldifferentiation,multicellularbehavior,andinteractionsbetweenmicroorganismsandtheireukaryotichosts.,醋酸纤维杆菌,NATuREREvIEws|MicrobiologyvoLuME7|APRIL2009|263,Principlesofc-di-GMPsignalling,DGC,PDE,Thebasicc-di-gMPsignallingmodule,Bindingofc-di-GMPtoasecondarysite(Isite)thatispresentinmostDGCsresultsinfeedbackproductinhibitionSpecificeffectors(proteinsorriboswitches),canbindc-di-GMPandsubsequentlyaffecttheregulatoryoutputofadirecttargetmoleculeorstructure.TargetscanbepromoterDNA(iftheeffectorisatranscriptionfactor),enzymesorcomplexcellularstructures,suchastheflagellarbasalbodyoranexopolysaccharidesynthesisandsecretionapparatus.,Itwasproposedthatthec-di-GMP-bindingIsiteinmanyGGDEFdomainscanalsobeaneffectorsite;ThatdedicatedeffectorproteinsmighthaveevolvedfromGGDEFdomainsinwhichtheAsitehasdegenerated,c-di-GMPisalsoaligandforariboswitch:theeffectorisaconservedRNAdomain(GEMM;RNAelementoccurringingenesfortheenvironment,membranesandmotility)thatispresentinthe5-untranslatedregionsofdifferentmRNAs.,GGDEFprotein-adi-guanylatecyclase,ReceiverdomainofRRfollowingbyGGDEFdomain(120aa)http:/www.sanger.ac.uk/Software/Pfam,EALprotein-ac-di-GMPphosphodiesterase,210aa,新月柄杆菌,Indeed,veryrecentfindingshaveshownthatthePilZdomainproteinYcgRofEscherichiacolicanbindcyclicdi-GMP,PilZ-C-di-GMPreceptor,c-di-GMPisrecognizedbyPilZdomain-containingreceptorsundergolarge-scaledomainrearrangem