Amino Terminal Domains of the NMDA Receptor Are Organized as Local Heterodimers 英文参考文献.docVIP

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Amino Terminal Domains of the NMDA Receptor Are Organized as Local Heterodimers 英文参考文献.doc

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Amino Terminal Domains of the NMDA Receptor Are Organized as Local Heterodimers 英文参考文献

AminoTerminalDomainsoftheNMDAReceptorAre OrganizedasLocalHeterodimers Chia-HsuehLee1,EricGouaux1,2* 1VollumInstitute,OregonHealthandScienceUniversity,Portland,Oregon,UnitedStatesofAmerica,2HowardHughesMedicalInstitute,OregonHealthandScience University,Portland,Oregon,UnitedStatesofAmerica Abstract The N-methyl-D-aspartate (NMDA) receptor, an obligate heterotetrameric assembly organized as a dimer of dimers, is typicallycomposedoftwoglycine-bindingGluN1subunitsandtwoglutamate-bindingGluN2subunits.Despitethecrucial rolethattheNMDAreceptorplaysinthenervoussystem,thespecificarrangementofsubunitswithinthedimer-of-dimer assemblageisnotconclusivelyknown.Herewestudiedtheorganizationoftheaminoterminaldomain(ATD)oftherat GluN1/GluN2AandGluN1/GluN2BNMDAreceptorsbycysteine-directed,disulfidebond-mediatedcross-linking.Wefound thatGluN1ATDsandGluN2ATDsspontaneouslyformeddisulfidebond-mediateddimersafterintroducingcysteinesinto the L1 interface of GluN2A or GluN2B ATD. The formation of dimer could be prevented by knocking out endogenous cysteineslocatedneartheL1interfaceofGluN1.TheseresultsindicatethatGluN1andGluN2ATDsformlocalheterodimers through the interactions in the L1-L1 interface and further demonstrate a dimer-of-heterodimer arrangement in GluN1/ GluN2AandGluN1/GluN2BNMDAreceptors. Citation:LeeC-H,GouauxE(2011)AminoTerminalDomainsoftheNMDAReceptorAreOrganizedasLocalHeterodimers.PLoSONE6(4):e19180.doi:10.1371/ journal.pone.0019180 Editor:Jo¨rgLangowski,GermanCancerResearchCenter,Germany ReceivedJanuary24,2011;AcceptedMarch29,2011;PublishedApril22,2011 Copyright: ? 2011 Lee, Gouaux. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This study was supported by National Institutes of Health and Howard Hughes Medical Institute. The funders had no role in study design, data collectionandanalysis,deci