Restoration of Proper Trafficking to the Cell Surface for Membrane Proteins Harboring Cysteine Mutations 英文参考文献.docVIP

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Restoration of Proper Trafficking to the Cell Surface for Membrane Proteins Harboring Cysteine Mutations 英文参考文献.doc

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Restoration of Proper Trafficking to the Cell Surface for Membrane Proteins Harboring Cysteine Mutations 英文参考文献

RestorationofProperTraffickingtotheCellSurfacefor MembraneProteinsHarboringCysteineMutations AngelicaLopez-Rodriguez,MiguelHolmgren* Neurophysiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda,Maryland,UnitedStatesofAmerica Abstract Acommonphenotypeformanygeneticdiseasesisthatthecellisunabletodeliverfull-lengthmembraneproteinstothe cellsurface.Forsomeformsofautism,hereditaryspherocytosisandcolorblindness,theculpritsaresinglepointmutations to cysteine. We have studied two inheritable cysteine mutants of cyclic nucleotide-gated channels that produce achromatopsia, a common form of severe color blindness. By taking advantage of the reactivity of cysteine’s sulfhydryl group,wemodifiedthesemutantswithchemicalreagentsthatattachmoietieswithsimilarchemistriestothewild-type aminoacids’sidechains.Weshowthatthesemodificationsrestoredproperdeliverytothecellmembrane.Oncethere,the channelsexhibitednormalfunctionalproperties.Thisstrategymightprovideauniqueopportunitytoassessthechemical natureofmembraneproteintrafficproblems. Citation:Lopez-RodriguezA,HolmgrenM(2012)RestorationofProperTraffickingtotheCellSurfaceforMembraneProteinsHarboringCysteineMutations.PLoS ONE7(10):e47693.doi:10.1371/journal.pone.0047693 Editor:RubenClaudioAguilar,PurdueUniversity,UnitedStatesofAmerica ReceivedJuly5,2012;AcceptedSeptember17,2012;PublishedOctober17,2012 Thisisanopen-accessarticle,freeofallcopyright,andmaybefreelyreproduced,distributed,transmitted,modified,builtupon,orotherwiseusedbyanyonefor anylawfulpurpose.TheworkismadeavailableundertheCreativeCommonsCC0publicdomaindedication. Funding:ThisworkwassupportedbytheIntramuralResearchProgramoftheNationalInstitutesofHealth,NationalInstituteNeurologicalDisordersandStroke. Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetingintere