Alternative Protein-Protein Interfaces Are Frequent Exceptions 英文参考文献.docVIP

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Alternative Protein-Protein Interfaces Are Frequent Exceptions 英文参考文献.doc

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Alternative Protein-Protein Interfaces Are Frequent Exceptions 英文参考文献

AlternativeProtein-ProteinInterfacesAreFrequent Exceptions TobiasHamp1,BurkhardRost1,2,3* 1TUM,Bioinformatik-I12,Informatik,Garching,Germany,2InstituteofAdvancedStudy(IAS),TUM,Garching,Germany,3DepartmentofBiochemistryandMolecular Biophysics,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica Abstract Theintricatemoleculardetailsofprotein-proteininteractions(PPIs)arecrucialforfunction.Therefore,measuringthesame interacting protein pair again, we expect the same result. This work measured the similarity in the molecular details of interactionforthesameandforhomologousproteinpairsbetweendifferentexperiments.Allscoresanalyzedsuggested thatdifferentexperimentsoftenfindexceptionsintheinterfacesofsimilarPPIs:upto22%ofallcomparisonsrevealedsome differencesevenforsequence-identicalpairsofproteins.Thecorrespondingnumberforpairsofclosehomologsreached 68%.Conversely, theinterfaces differedentirely for12–29%of allcomparisons. All theseestimates werecalculatedafter redundancyreduction.Themagnitudeofinterfacedifferencesrangedfromsubtletotheextreme,asillustratedbyafew examples. An extreme case was a change of the interacting domains between two observations of the same biological interaction. One reason for different interfaces was the number of copies of an interaction in the same complex: the probabilityofobservingalternativebindingmodesincreaseswiththenumberofcopies.Evenafterremovingthespecial cases with alternative hetero-interfaces to the same homomer, a substantial variability remained. Our results strongly supportthesurprisingnotionthattherearemanyalternativesolutionstomaketheintricatemoleculardetailsofPPIscrucial forfunction. Citation: Hamp T, Rost B (2012) Alternative Protein-Protein Interfaces Are Frequent Exceptions. PLoS Comput Biol 8(8): e1002623. doi:10.1371/ journal.pcbi.1002623 Editor:RuthNussinov,NationalCancerInstitute,UnitedStatesofAmericaandTelAvivUniversity,Israel ReceivedOctober28,2011;AcceptedJune11,2012;PublishedAugust2,2012 Copyright: ? 2012 Ha