Protein Homology Network Families Reveal Step-Wise Diversification of Type III and Type IV Secretion Systems 英文参考文献.docVIP

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Protein Homology Network Families Reveal Step-Wise Diversification of Type III and Type IV Secretion Systems 英文参考文献.doc

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Protein Homology Network Families Reveal Step-Wise Diversification of Type III and Type IV Secretion Systems 英文参考文献

ProteinHomologyNetworkFamiliesReveal Step-WiseDiversificationofTypeIII andTypeIVSecretionSystems Duccio Medini, Antonello Covacci*,Claudio Donati CellularMicrobiologyandBioInformaticsUnit,NovartisVaccinesandDiagnostics,Siena,Italy Fromtheanalysisof251prokaryoticgenomesstoredinpublicdatabases,the761,260deducedproteinswereusedto reconstruct a complete set of bacterial proteic families. Using the new Overlap algorithm, we have partitioned the ProteinHomologyNetwork(PHN),wheretheproteinsarethenodesandthelinksrepresenthomologyrelationships. ThealgorithmidentifiesthedenselyconnectedregionsofthePHNthatdefinethefamiliesofhomologousproteins, herecalledPHN-Families,recognizingthephylogeneticrelationshipsembeddedinthenetwork.Bydirectcomparison withamanuallycurateddataset,weassessedthatthisclassificationalgorithmgeneratesdataofqualitysimilartoa humanexpert.Then,weexplored thenetworktoidentify familiesinvolved intheassembly ofTypeIIIandTypeIV secretion systems (T3SS and T4SS). We noticed that, beside a core of conserved functions (eight proteins for T3SS, sevenforT4SS),avariablesetofaccessorycomponentsisalwayspresent(onetonineforT3SS,onetofiveforT4SS). EachmemberofthecorecorrespondstoasinglePHN-Family,whileaccessoryproteinsaredistributedamongdifferent purefamilies.ThePHN-FamilyclassificationsuggeststhatT3SSandT4SShavebeenassembledthroughastep-wise, discontinuousprocess,bycomplementingtheconservedcorewithsubgroupsofnonconservedproteins.Suchgenetic modules,independentlyrecruitedandprobablytunedonspecificeffectors,contributetothefunctionalspecialization oftheseorganellestodifferentmicroenvironments. Citation:MediniD,CovacciA,DonatiC(2006)Proteinhomologynetworkfamiliesrevealstep-wisediversificationofTypeIIIandTypeIVsecretionsystems.PLoSComputBiol 2(12):e173.doi:10.1371/journal.pcbi.0020173 We have used the intrinsic transitivity of true homology relationships to de?ne a new similarity measure among Introduction TheseminalobservationofMargarethO.Dayhoff[1,2]that proteinsevolve