Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters 英文参考文献.docVIP

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Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters 英文参考文献.doc

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Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters 英文参考文献

EvolutionaryDescentofPrionGenesfromtheZIPFamily ofMetalIonTransporters GeroldSchmitt-Ulms1,2*,SepehrEhsani1,2,JoelC.Watts1,2,3,DavidWestaway5,HolgerWille3,4 1CentreforResearchinNeurodegenerativeDiseases,UniversityofToronto,Toronto,Ontario,Canada,2DepartmentofLaboratoryMedicineandPathobiology,University ofToronto,Toronto,Ontario,Canada,3InstituteforNeurodegenerativeDiseases,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica, 4DepartmentofNeurology,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica,5CentreforPrionsandProteinFoldingDiseases, UniversityofAlberta,Edmonton,Alberta,Canada Abstract Inthemorethantwentyyearssinceitsdiscovery,boththephylogeneticoriginandcellularfunctionoftheprionprotein (PrP)haveremainedenigmatic.InsightsintoapossiblefunctionofPrPmaybeobtainedthroughthecharacterizationofits molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transportersoftheZIPfamily,ZIP6andZIP10,tomammalianprionproteinsinvivo.Asubsequentbioinformaticanalysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species placethesplitfromtheZIP-likeancestorgeneatthebaseofthechordatelineage.Thisrelationshipexplainsstructuraland functionalfeaturesfoundwithinmammalianprionproteinsaselementsofanancientinvolvementinthetransmembrane transportofdivalentcations.ThephylogeneticandspatialconnectiontoZIPproteinsisexpectedtoopennewavenuesof researchtoelucidatethebiologyoftheprionproteininhealthanddisease. Citation:Schmitt-UlmsG,EhsaniS,WattsJC,WestawayD,WilleH(2009)Ev