Promiscuous Binding in a Selective Protein The Bacterial Na+H+ Antiporter 英文参考文献.docVIP

PromiscuousBindinginaSelectiveProtein:TheBacterial Na /H Antiporter + + RaphaelAlhadeff.,AssafGanoth.,MiriamKrugliak,IsaiahT.Arkin* DepartmentofBiologicalChemistry,TheAlexanderSilbermanInstituteofLifeSciences,TheHebrewUniversityofJerusalem,Jerusalem,Israel Abstract Theabilitytodiscriminatebetweenhighlysimilarsubstratesisoneoftheremarkablepropertiesofenzymes.Forexample, transporters and channels that selectively distinguish between various solutes enable living organisms to maintain and control their internal environment in the face of a constantly changing surrounding. Herein, we examine in detail the selectivity properties of one of the most important salt transporters: thebacterial Naz/Hz antiporter. Selectivity canbe achieved at either the substrate binding step or in subsequent antiporting. Surprisingly, using both computational and experimentalanalysessynergistically,weshowthatbindingperseisnotasufficientdeterminantofselectively.Allalkaliions fromLiztoCszwereabletocompetitivelybindtheantiporter’sbindingsite,whethertheproteinwascapableofpumping themornot.Hence,weproposethatNhaA’sbindingsiteisrelativelypromiscuousandthattheselectivityisdeterminedata laterstageofthetransportcycle. Citation:AlhadeffR,GanothA,KrugliakM,ArkinIT(2011)PromiscuousBindinginaSelectiveProtein:TheBacterialNa+/H+Antiporter.PLoSONE6(10):e25182. doi:10.1371/journal.pone.0025182 Editor:EugeneA.Permyakov,RussianAcademyofSciences,InstituteforBiologicalInstrumentation,RussianFederation ReceivedAugust8,2011;AcceptedAugust26,2011;PublishedOctober12,2011 Copyright: ? 2011 Alhadeff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported in part by grants from The Rudin Fellowship Trust (to RA), The Lady Davis Fellowship Trust and The Valazzi-Pikovsky FellowshipFund(toAG),andtheIsraeliScienceFoundat