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Molecular Evolution and Structural Features of IRAK Family Members 英文参考文献.doc

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Molecular Evolution and Structural Features of IRAK Family Members 英文参考文献

MolecularEvolutionandStructuralFeaturesofIRAK FamilyMembers VijayakumarGosu,ShaherinBasith,PrasannavenkateshDurai,SangdunChoi* DepartmentofMolecularScienceandTechnology,AjouUniversity,Suwon,Korea Abstract Theinterleukin-1receptor-associatedkinase(IRAK)familycomprisescriticalsignalingmediatorsoftheTLR/IL-1Rsignaling pathways.IRAKsareSer/Thrkinases.Thereare4membersinthevertebrategenome(IRAK1,IRAK2,IRAKM,andIRAK4)and an IRAK homolog, Pelle, in insects. IRAK family members are highly conserved in vertebrates, but the evolutionary relationshipbetweenIRAKsinvertebratesandinsectsisnotclear.Toinvestigatetheevolutionaryhistoryandfunctional divergenceofIRAKmembers,weperformedextensivebioinformaticsanalysis.ThephylogeneticrelationshipbetweenIRAK sequences suggests that gene duplication events occurred in the evolutionary lineage, leading to early vertebrates. A comparativephylogeneticanalysiswithinsecthomologsofIRAKssuggeststhattheTubeproteinisahomologofIRAK4, unliketheanticipatedprotein,Pelle.Furthermore,theanalysissupportsthatanIRAK4-likekinaseisanancestralproteinin themetazoanlineageoftheIRAKfamily.Throughfunctionalanalysis,severalpotentiallydivergedsiteswereidentifiedin thecommondeathdomainandkinasedomain.Thesesiteshavebeenconstrained duringevolutionbystrong purifying selection,suggestingtheirfunctionalimportancewithinIRAKs.Insummary,ourstudyhighlightedthemolecularevolution oftheIRAKfamily,predictedtheaminoacidsthatcontributedtofunctionaldivergence,andidentifiedstructuralvariations amongtheIRAKparalogsthatmayprovideastartingpointforfurtherexperimentalinvestigations. Citation:GosuV,BasithS,DuraiP,ChoiS(2012)MolecularEvolutionandStructuralFeaturesofIRAKFamilyMembers.PLoSONE7(11):e49771.doi:10.1371/ journal.pone.0049771 Editor:VladimirN.Uversky,UniversityofSouthFloridaCollegeofMedicine,UnitedStatesofAmerica ReceivedJuly31,2012;AcceptedOctober12,2012;PublishedNovember14,2012 Copyright: ? 2012 Gosu et al. This is an open-access article distributed under the terms of th