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1、IDENTIFICATIONANDFUNCTIONSOFUSEFULLYDISORDEREDPROTEINSBYA.KEITHDUNKER,CELESTEJ.BROWNANDSchoolofMolecularBiosciencesWashingtonStateUniversity,Pullman,WA99164-4660ZORANOBRADOVIĆCenterforInformationScienceandTechnology,TempleUniversity,Philadelphia,PA19122I.TestingWhetherIntrin
2、sicDisorderisEncodedbytheAminoAcidSequenceA.UsingPredictionB.DatabaseComparisonsII.PredictionofOrderandDisorderfromAminoAcidSequenceA.PredictorsofNaturalDisorderedRegions(PONDRs)B.PONDRAccuraciesIII.PONDREstimationsoftheCommonnessofIntrinsicallyDisorderedProteinsIV.Functions
3、ofIntrinsicallyDisorderedProteinV.ConclusionsReferencesNumerousapparentlynativeproteinshavedisorderedregionsandsomearewhollydisordered,yetbothtypesofproteinoftenutilizetheirunorderedaminoacidstocarryoutfunction.Howdosuchdisorderedproteinsfitintotheviewthataminoacidsequenceco
4、desforproteinstructure?Ourhypothesiswasthatdisorder,likeorder,isencodedbytheaminoacidsequence.Totestthishypothesis,intrinsicallydisorderedproteinwascomparedwithorderedprotein.Initially,smallsetsoforderedanddisorderedsequenceswerecomparedbypredictionoforderanddisorder.Success
5、ratesmuchgreaterthanexpectedbychanceindicatedthatdisorderisencodedbythesequence.Oncelargerdatasetsoforderedanddisorderedproteinswerecollected,directsequencecomparisonscouldbemade.Theaminoacidcompositions,sequenceattributes,andevolutionarycharacteristicsofdisorderedsequencesd
6、ifferedfromthecorrespondingfeaturesoforderedsequencesinwayscommensuratewithourhypothesisthatdisorderisencodedbythesequence.Thedifferencesbetweenorderedanddisorderedsequencesenabledthedevelopmentofpredictorsofnaturaldisorderedregions(PONDRs).Sincesequencecodesforstructureands
7、incesequencecodesfordisorder,itfollowsthatdisorderoughttobeconsideredacategoryofnativeproteinstructure.Twoquestionsarisefromthiscategorization:howcommonisnativeproteindisorderandwhatfunctionsarecarriedoutbythiscategoryofstructure?ApplicationofaparticularPONDRtogenomicsetsofs
8、equencesindicatedthatdisorderedregionsareextremelycommon,especiallyineukary
