Putting into Practice Domain-Linear Motif Interaction Predictions for Exploration of Protein Networks 英文参考文献.docVIP

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Putting into Practice Domain-Linear Motif Interaction Predictions for Exploration of Protein Networks 英文参考文献.doc

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Putting into Practice Domain-Linear Motif Interaction Predictions for Exploration of Protein Networks 英文参考文献

PuttingintoPracticeDomain-LinearMotifInteraction PredictionsforExplorationofProteinNetworks KatjaLuck1,SadekFournane1,BrunoKieffer2,MurielleMasson1,YvesNomine′1,GillesTrave′1* 1GroupOnco-Proteins,InstitutdeRecherchedel’EcoledeBiotechnologiedeStrasbourg,1,BP10413,Illkirch,France,2BiomolecularNMRgroup,InstitutdeGe′ne′tiqueet deBiologieMole′culaire etCellulaire,1,BP10413,Illkirch,France Abstract PDZdomainsrecogniseshortsequencemotifsattheextremeC-terminiofproteins.Amodelbasedonmicroarraydatahas beenrecentlypublishedforpredictingthebindingpreferencesofPDZdomainstofiveresiduelongC-terminalsequences. HereweinvestigatedthepotentialofthispredictorfordiscoveringnovelproteininteractionsthatinvolvePDZdomains. Whentestedonrealnegativedataassembledfrompublishedliterature,thepredictordisplayedahighfalsepositiverate (FPR).WepredictedandexperimentallyvalidatedinteractionsbetweenfourPDZdomainsderivedfromthehumanproteins MAGI1andSCRIBand19peptidesderivedfromhumanandviralC-terminiofproteins.Measuredbindingintensitiesdidnot correlatewithpredictionscores,andthehighFPRofthepredictorwasconfirmed.Resultsindicatethatlimitationsofthe predictormayarisefromanincompletemodeldefinitionandimpropertrainingofthemodel.Takingintoaccountthese limitations,weidentifiedseveralnovelputativeinteractionsbetweenPDZdomainsofMAGI1andSCRIBandtheC-terminiof theproteinsFZD4,ARHGAP6,NET1,TANC1,GLUT7,MARCH3,MAS,ABC1,DLL1,TMEM215andCYSLTR2.Theseproteinsare localisedtothemembraneorsuggestedtoactclosetoitandareofteninvolvedinGproteinsignalling.Furthermore,we showed that, while extension of minimal interacting domains or peptides toward tandem constructs or longer peptides never suppressed their ability to interact, the measured affinities and inferred specificity patterns often changed significantly.Thissuggeststhatifproteinfragmentsinteract,thefulllengthproteinsarealsolikelytointeract,albeitpossibly with altered affinities and specificities. Therefore, predictors dealing with protein fragments are promising tools