简介：蛋白质领域被保存，在相互作用起一个重要作用在之中的机能上地独立的结构联系了蛋白质。域域相互作用最近被用来预言蛋白质蛋白质相互作用(PPI)。一般来说，一双领域的相互作用概率用训练得分功能被获得。令人满意阀值，当“交往”，带那些领域的蛋白质对被考虑。在这研究，蛋白质的签名内容被利用在Saccharomycescerevisiae，Caenorhabditiselegin，和人预言PPI对现代人。蛋白质签名模式的类似被获得，PPI预言基于二进制类似得分函数被拉。结果证明由建议途径的预言的真积极的率用最大的可能性评价方法比那高是约32%，导致在与一个测试集合相比操作的接收装置下面的区域的22%增加什么时候特征(巨鸟)曲线。当包含一个或二签名的蛋白质被移开时，预言的PPI对的敏感显著地增加了。预言的PPI对是平均，11更多半预定在0.95的信心水平比随机的选择交往，并且平均，4比那些由也预言更好预定种系发生的介绍或基因表达介绍。

简介：TheE(envelope)proteinisthesmalleststructuralproteininallcoronavirusesandistheonlyviralstructuralproteininwhichnovariationhasbeendetected.WeconductedgenomesequencingandphylogeneticanalysesofSARS-CoV.Basedongenomesequencing,wepredictedtheEproteinisatransmembrane(TM)pro-teincharacterizedbyaTMregionwithstronghydrophobicityandα-helixcon-formation.Weidentifiedasegment(NH2-_L-Cys-A-Y-Cys-Cys-N_-COOH)inthecarboxyl-terminalregionoftheEproteinthatappearstoformthreedisulfidebondswithanothersegmentofcorrespondingcysteinesinthecarboxyl-terminusoftheS(spike)protein.ThesebondspointtoapossiblestructuralassociationbetweentheEandSproteins.OurphylogeneticanalysesoftheEproteinsequencesinallpub-lishedcoronavirusesplaceSARS-CoVinanindependentgroupinCoronaviridaeandsuggestanon-humananimalorigin.

简介：管理生命的自然现象的内在的原则是在最近的年里收到到期的重要性的关键问题之一。没有规模的建筑学的特色是大多数连接节点(中心)的活力。这篇文章的主要目的是由在二个相互作用系统的拓扑的参数上考虑建筑上的模式和中心的移动的后果分析蛋白质蛋白质和果蝇melanogaster的新陈代谢的相互作用网络。分析证明两个相互作用网络跟随一个没有规模的模型，建立从改变的状况，很真实的世界网络遵循小世界模式的事实。平均路径长度出现了一双重并且三方面的增加(从9.42～20.93并且从5.29～17.75变化，分别地)分别地，由于中心的删除为蛋白质蛋白质和新陈代谢的相互作用联网。相反，节点的任意的消除没在蛋白质蛋白质和新陈代谢的相互作用网络的拓扑的参数显示出任何显著不同(平均路径长度：9.42+/-0.02和5.27+/-0.01，分别地)。为二个盒子的这越轨行为强调大多数连接节点的意义到网络的自然拓扑学。

简介：Protein-proteininteractions(PPIs)havebeenwidelystudiedtounderstandthebiologicalprocessesormolecularfunctionsassociatedwithdifferentdiseasesystemslikecancer.Whilefocusedstudiesonindividualcancershavegeneratedvaluableinformation,globalandcomparativeanalysisofdatasetsfromdifferentcancertypeshasnotbeendone.Inthiswork,wecarriedoutbioinformaticanalysisofPPIscorrespondingtodifferentiallyexpressedgenesfrommicroarraysofvarioustumortissues(belongingtobladder,colon,kidneyandthyroidcancers)andcomparedtheirassociatedbiologicalprocessesandmolecularfunctions(basedonGeneOntologyterms).Weidentifiedasetofprocessesorfunctionsthatarecommontoallthesecancers,aswellasthosethatarespecifictoonlyoneorpartialcancertypes.Similarly,proteininteractionnetworksinnucleicacidmetabolismwerecomparedtoidentifythecommon/specificclustersofproteinsacrossdifferentcancertypes.Ourresultsprovideabasisforfurtherexperimentalinvestigationstostudyproteininteractionnetworksassociatedwithcancer.Themethodologydevelopedinthisworkcanalsobeappliedtostudysimilardiseasesystems.

简介：ProteinkinaseRAFisstrategicallylocatedinthe'Ras-MAP-kinasesignaltransductionpathway',aprinciplesystemwhichtransmitssignalsfromgrowthfactorreceptorstothenucleus,resultingincellproliferation.GrowthfactorresponsesaremediatedinpartbyactivationofRas,whichinturnactivatesRAFtophosphorylateMEK,itsdownstreamsubstrate.MEKactivatesMAPkinasetoinfluencenuclearevents.itisclear.however,thatanetworkofsignalsotherthanthosecarredbyRasplaysaroleinRAFregulation.Theseorthogonalinfluencesaremediatedbu:serine/threoninekinases,tyrosinekinases,andprotein-proteininteractions.AsafurthercomplicationtotheRAFnetwork,threeisoformsofRAFhavebeenestablishedwhichhavedivergentN-terminalregulatorydomains,Whereasthesedivergentregulatorydomainsimplicateisoform-specificfunctions,noclearevidenceorhypothesisfordistinctfunctionsforindividualisoformshasbeenpresented.Recently,'isoform-specificproteininteractions'havebeenidentifiedamongnumerousproteinsinteractingwithRAF,ThesestudiesmayservetodelineateindependentfunctionsforRAFisoforms.

简介：植物蛋白质蛋白质相互作用网络没被大规模实验识别了。以便更好在米饭理解蛋白质相互作用，预言的米饭Interactome网络(PRIN；http://bis.zju.edu.cn/prin/)介绍76,585个预言的相互作用包含5,049米饭蛋白质。在印射米饭的genomic特征以后(去注解，subcellular本地化预言，和基因表示)，我们发现一个注解得好、生物学上重要的网络是足够富有的在高顺序的生物系统以内捕获许多重要功能的连接，例如小径和生物进程。而且，我们作为例子拿了疯盒子的包含域的蛋白质和生理节奏的节奏发信号小径证明功能的蛋白质建筑群和生物小径能有效地在我们的预言的网络被扩展。在PRIN的扩展分子的网络更加改进了这些分析的能力集成存在知识并且提供新奇卓见进基因和基因网络的功能和协作。

简介：蜕皮激素受体(EcR)和ultraspiracle(USP)形成heterodimers调停ecdysteroid在molting和变形期间发信号。各种各样的EcR/USPheterodimers被报导了。然而，联合什么样的EcR/USP被鳞翅类的昆虫在幼虫蛹的变形期间采用并且EcR/USPheterodimer是否在不同纸巾之中变化，是不清楚的。探讨这些问题，每EcR和USP的二isoforms从普通糖蛾被克隆，他们的送信人RNA表示模式被即时量的聚合酶链反应响应神经质的正式就职在幼虫蛹的变形期间并且在midgut在不同纸巾检验。而且，他们的subcellular本地化和蛋白质蛋白质相互作用被短暂表示并且分别地的远西方的弄污探索。所有四基因在prepuae或蛹是显著地起来调整的。EcRB1和USP1的表示侧面与在外皮，胖身体和midgut的对方将近相同，并且一种类似的状况也适用于EcRA和USP2。三基因除了USP2，和USP1回答了正式就职到20-hydroxyecdysone(20E)能由20E和少年荷尔蒙起来调整。在原子核和原子本地化主要局部性的四蛋白质被20E支持。在每EcR和USP之间的蛋白质蛋白质相互作用在vitro被发现。这些结果建议EcR/USPheterodimer(EcRA/USP2和EcRB1/USP1)的二种类型可以在普通糖蛾同时存在，并且后者应该在幼虫蛹的变形期间起更重要的作用。另外，EcR/USPheterodimer的类型不在在变形期间经历histolysis和新生的纸巾变化。

简介：ThenameofSRproteinsisderivedfromtheirtypicalRSdomainthatisrichinserine(Ser,S)andarginine(Arg,R).Theyareconservedinevolution.Uptonow,10membersoftheSRproteinfamilyhavebeenidentifiedinhumans.SRproteinscontainoneortwoRNAbindingmotifsasidefromtheRSdomain,andalsopossessspecialbiochemicalandimmunologicalfeatures.AstothefunctionsofSRproteins,theyfacilitatetherecruitmentofthecomponentsofsplicesomeviaprotein-proteininteractiontoprompttheassemblyofearlysplicesome;whileinalternativesplicing,tissue-specificallyexpressedSRproteinalongwiththerelativeratioofSRproteinandheterogeneousnuclearribonucleoprotein(hnRNP)iscomposedoftwomainregulativemechanismsforalternativesplicing.Almostallofthebiochemicalfunctionsareregulatedbyreversiblephosphorylation.

简介：WedescribetheGALT-Protdatabaseanditsrelatedweb-basedapplicationthathavebeendevelopedtocollectinformationaboutthestructuralandfunctionaleffectsofmutationsonthehumanenzymegalactose-1-phosphateuridyltransferase(GALT)involvedinthegeneticdiseasenamedgalactosemiatypeI.Besidesalistofmissensemutationsatgeneandproteinsequencelevels,GALT-ProtreportstheanalysisresultsofmutantGALTstructures.Inadditiontothestructuralinformationaboutthewild-typeenzyme,thedatabasealsoincludesstructuresofover100singlepointmutantssimulatedbymeansofacomputationalprocedure,andtheanalysistoeachmutantwasmadewithseveralbioinformaticsprogramsinordertoinvestigatetheeffectofthemutations.Theweb-basedinterfaceallowsqueryingofthedatabase,andseverallinksarealsoprovidedinordertoguaranteeahighintegrationwithotherresourcesalreadypresentontheweb.Moreover,thearchitectureofthedatabaseandthewebapplicationisflexibleandcanbeeasilyadaptedtostoredatarelatedtootherproteinswithpointmutations.GALT-Protisfreelyavailableathttp://bioinformatica.isa.cnr.it/GALT/.

简介：Inthepost-genomicera,variouscomputationalmethodsthatpredictprotein-proteininteractionsatthegenomelevelareavailable;however,eachmethodhasitsownadvantagesanddisadvantages,resultinginfalsepredictions.Herewedevel-opedauniqueintegratedapproachtoidentifyinteractingpartner(s)ofSemaphorin5A(SEMA5A),beginningwithsevenproteinssharingsimilarligandinteractingresiduesasputativebindingpartners.ThemethodsincludeDwyerandRoot-Bernstein/Dillontheoriesofproteinevolution,hydropathiccomplementarityofproteinstructure,patternofproteinfunctionsamongmolecules,informationondomain-domaininteractions,co-expressionofgenesandproteinevolution.AmongthesetofsevenproteinsselectedasputativeSEMA5Ainteractingpartners,wefoundthefunctionsofPlexinB3andNeuropilin-2tobeassociatedwithSEMA5A.WemodeledthesemaphorindomainstructureofPlexinB3andfoundthatitsharessimilaritywithSEMA5A.Moreover,avirtualexpressiondatabasesearchandRT-PCRanalysisshowedco-expressionofSEMA5AandPlexinB3andtheseproteinswerefoundtohaveco-evolved.Inaddition,weconfirmedtheinterac-tionofSEMA5AwithPlexinB3inco-immunoprecipitationstudies.Overall,thesestudiesdemonstratethatanintegratedmethodofpredictioncanbeusedatthegenomelevelfordiscoveringmanyunknownproteinbindingpartnerswithknownligandbindingdomains.

简介：Venomousanimalsontheearthhavebeenfoundtobevaluableresourcesforthedevelopmentoftherapeutics.Enzymaticandnon-enzymaticproteinsandpeptidesarethemajorcomponentsofanimalvenoms,manyofwhichcantargetvariousionchannels,receptors,andmembranetransporters.Comparedtotraditionalsmallmoleculedrugs,naturalproteinsandpeptidesexhibithigherspecificityandpotencytotheirtargets.Inthisreview,wesummarizethevarietiesandcharacteristicsoftoxinsfromafewrepresentativevenomousanimals,anddescribethecomponentsandapplicationsofanimaltoxinsaspotentialdrugcandidatesinthetreatmentofhumandiseases,includingcancer,neurodegenerativediseases,cardiovasculardiseases,neuropathicpain,aswellasautoimmunediseases.Inthemeantime,therearemanyobstaclestotranslatenewtoxindiscoverytotheirclinicalapplications.Thechallenges,strategies,andperspectivesinthedevelopmentoftheproteintoxin-baseddrugsarediscussedaswell.

简介：Proteinphosphorylationplaysanimportantroleinvariouscellularprocesses.Duetoitshighcomplexity,themechanismneedstobefurtherstudied.Inthelastfewyears,manymethodshavebeencontributedtothisfield,butalmostalloftheminvestigatedthemechanismbasedonproteinsequencesaroundproteinsites.Inthisstudy,weimplementanexplorationbycharacterizingthemicroenvironmentsurroundingphosphorylatedproteinsiteswithamodifiedshellmodel,andobtainsomesignificantpropertiesbytherank-sumtest,suchasthelackofsomeclassesofresidues,atoms,andsecondarystructures.Furthermore,wefindthatthedepletionofsomepropertiesaffectsproteinphosphorylationremarkably.Ourresultssuggestthatitisameaningfuldirectiontoexplorethemechanismofproteinphosphorylationfrommicroenvironmentandweexpectfurtherfindingsalongwiththeincreasingsizeofphosphorylationandproteinstructuredata.

简介：Thereisaccumulatingevidencethatcysteinesulfenation（cys-SOH）inproteinsplaysanimportantroleincellularresponsetooxidativestress.Thepurposeofthepresentstudywastoidentifymitochondrialproteinsthatundergochangesincys-SOHduringaging.Studieswereconductedinratswhentheywere5or30monthsofage.FollowingblockingoffreeproteinthiolswithN-ethylmaleimide,proteinsulfenicacidswerereducedbyarsenitetofreethiolgroupsthatweresubsequentlylabeledwithbiotin-maleimide.Sampleswerethencomparativelyanalyzedbytwo-dimensionalWesternblots,andproteinsshowingchangesinsulfenationwereselectivelyidentifiedbymassspectrometrypeptidesequencing.Asaresult,fiveproteinswereidentified.Proteinsshowinganage-relateddecreaseinsulfenationincludepyruvatecarboxylaseandpyruvatedehydrogenase;whilethoseshowinganage-relatedincreaseinsulfenationincludeaconitase,mitofilin,andtubulin（α-1）.Resultsofthepresentstudyprovideageneralpictureofmitochondrialproteinsulfenationinbrainoxidativestressandimplicatetheinvolvementofproteinsulfenationinoveralldeclineofmitochondrialfunctionduringbrainaging.

简介：Thenucleocapsidprotein(Nprotein)hasbeenfoundtobeanantigenicproteininanumberofcoronaviruses.WhethertheNproteininsevereacuterespiratorysyndrome-associatedcoronavirus(SARS-CoV)isantigenicremainstobeelucidated.UsingWesternblotandEnzyme-linkedImmunosorbentAssay(ELISA),therecombinantNproteinsandthesynthesizedpeptidesderivedfromtheNproteinwerescreenedinserafromSARSpatients.AllpatientserainthisstudydisplayedstrongpositiveimmunoreactivitiesagainsttherecombinantNproteins,whereasnormalseragavenegativeimmunoresponsestotheseproteins,indicatingthattheNproteinofSARS-CoVisanantigenicprotein.Furthermore,theepitopesitesintheNproteinweredeterminedbycompetitionexperiments,inwhichtherecombinantproteinsorthesynthesizedpeptidescompetedagainsttheSARS-CoVproteinstobindtotheantibodiesraisedinSARSsera.OneepitopesitelocatedattheC-terminuswasconfirmedasthemostantigenicregioninthisprotein.AdetailedscreeningofpeptidewithELISAdemonstratedthattheaminosequencefromCodons371to407wastheepitopesiteattheC-terminusoftheNprotein.UnderstandingoftheepitopesitescouldbeverysignificantfordevelopinganeffectivediagnosticapproachtoSARS.

简介：Functionalcharacterizationofeverysingleproteinisamajorchallengeofthepostgenomicera.Thelarge-scaleanalysisofacell'sproteins,proteomics,seekstoprovidetheseproteinswithreliableannotationsregardingtheirinteractionpartnersandfunctionsinthecellularmachinery.Animportantsteponthiswayistodeterminethesubcellularlocalizationofeachprotein.Eukaryoticcellsaredividedintosubcellularcompartments,ororganelles.Transportacrossthemembraneintotheorganellesisahighlyregulatedandcomplexcellularprocess.Predictingthesubcellularlocalizationbycomputationalmeanshasbeenanareaofvividactivityduringrecentyears.Thepubliclyavailablepredictionmethodsdiffermainlyinfouraspects:theunderlyingbiologicalmotivation,thecomputationalmethodused,localizationcoverage,andreliability,whichareofimportancetotheuser.Thisreviewprovidesashortdescriptionofthemaineventsintheproteinsortingprocessandanoverviewofthemostcommonlyusedmethodsinthisfield.

简介：Numerouscellularfunctionsoccurinspatiallyandtemporallyconfinedregions.Recentstudieshaveshownthatmembrane-lessorganellesandcompartmentsinthecellareassembledvialiquid-liquidphaseseparation(LLPS).InvitroLLPSassaysusingrecombinantexpressedandpurifiedproteinsarenecessaryforustofurtherunderstandhowtheassemblyofphase-separatedcompartmentsisregulatedincells.However;uniformstandardsandprotocolsarelackingfortheseinvitrostudies.Here,wedescribeastep-by-stepprotocolcommonlyusedtoinvestigateinvitroLLPSusingpurifiedproteins.Thisprotocolincludesexpressionandpurificationofthestudiedproteins,inductionofLLPSofthepurifiedproteins,andstudiesofthebiophysicalpropertiesoftheliquiddropletsformedbyLLPS.TheseprotocolscanbeeasilyfollowedbyresearcherstoinvestigatetheLLPSbehaviorsofproteinsofinterest.

简介：Anewmethodwasdescribedforusingarecurrentneuralnetworkwithbiasunitstopredictcontactmapsinproteins.Themaininputstotheneuralnetworkincluderesiduespairwise,residueclassificationaccordingtohydrophobicity,polar,acidic,basicandsecondarystructureinformationandresidueseparationbetweentworesidues.Inourwork,adatasetwasusedwhichwascomposedof53globulinproteinsofknown3Dstructure.Anaveragepredictiveaccuracyof0.29wasobtained.Ourresultsdemonstratetheviabilityoftheapproachforpredictingcontactmaps.

简介：Usingatriangularlatticemodeltostudythedesignabilityofproteinfolding,weovercametheparityproblemofpreviouscubiclatticemodelandenumeratedallthesequencesandcompactstructuresonasimpletwo-dimensionaltriangularlatticemodelofsize4+5+6+5+4.Weusedtwotypesofaminoacids,hydrophobicandpolar,tomakeupthesequences,andachieved223+212differentsequencesexcludingthereversesymmetrysequences.Thetotalstringnumberofdistinctcompactstructureswas219,093,excludingreflectionsymmetryintheself-avoidingpathoflength24triangularlatticemodel.Basedonthismodel,weappliedafastsearchalgorithmbyconstructingaclustertree.Thealgorithmdecreasedthecomputationbycomputingtheobjectiveenergyofnon-leafnodes.Theparallelexperimentsprovedthatthefasttreesearchalgorithmyieldedanexponentialspeed-upinthemodelofsize4+5+6+5+4.Designabilityanalysiswasperformedtounderstandthesearchresult.

简介：Thecorona-likespikesorpeplomersonthesurfaceofthevirionunderelectronicmicroscopearethemoststrikingfeaturesofcoronaviruses.TheS(spike)proteinisthelargeststructuralprotein,with1,255aminoacids,intheviralgenome.Itsstructurecanbedividedintothreeregions:alongN-terminalregionintheexte-rior,acharacteristictransmembrane(TM)region,andashortC-terminusintheinteriorofavirion.WedetectedfifteensubstitutionsofnucleotidesbycomparisonswiththeseventeenpublishedSARS-CoVgenomesequences,eight(53.3%)ofwhicharenon-synonymousmutationsleadingtoaminoacidalternationswithpredictedphysiochemicalchanges.ThepossibleantigenicdeterminantsoftheSproteinarepredicted,andtheresultisconfirmedbyELISA(enzyme-linkedimmunosorbentassay)withsynthesizedpeptides.AnotherprofoundfindingisthatthreedisulfidebondsaredefinedattheC-terminuswiththeN-terminusoftheE(envelope)pro-tein,basedonthetypicalsequenceandpositions,thusestablishingthestructuralconnectionwiththesetwoimportantstructuralproteins,ifconfirmed.Phyloge-neticanalysisrevealsseveralconservedregionsthatmightbepotentdrugtargets.

简介：Humanpolymorphonuclearleukocytes(PMN)havebeenreportedtocompletelylackofDNA-dependentproteinkinase(DNA-PK)whichiscomposedofKuproteinandthecatalyticsubunitDNA-PKcs,neededfornonhomologousend-joining(NHEJ)ofDNAdouble-strandbreaks.PromyelocyticHL-60cellsexpressavariantformofKuresultinginenhancedradiationsensitivity.ThisraisesthequestioniflowefficiencyofNHEJ,instrumentalforthecellularrepairofoxidativedamage,isanormalcharacteristicofmyeloiddifferentiation.HereweconfirmedthecompletelackofDNAPKinPMNproteinextracts,andtheexpressionofthetruncatedKu86variantforminHL-60.However,thisdegradationofDNA-PKwasshowntobeduetoaDNA-PK-degradingproteaseinPMNandHL-60.Inaddition,byusingaprotease-resistantwholecellassay,bothKu86andDNA-PKcscouldbedemonstratedinPMN,suggestingthepreviouslyreportedabsenceinPMNofDNA-PKtobeanartefact.ThelevelsofKu86andDNA-PKcsweremuchreducedinPMN,ascomparedwiththatofthelymphocytes,whereasHL-60displayedamarkedlyelevatedDNA-PKconcentration.Inconclusion,ourfindingsprovideevidenceofreduced,notdepletedexpressionofDNA-PKduringthematurestagesofmyeloiddifferentiation.