Mg2+ in the Major Groove Modulates B-DNA Structure and Dynamics 英文参考文献.docVIP

Mg2+intheMajorGrooveModulatesB-DNAStructure andDynamics MarcGue′roult1,2,OlivierBoittin1,OliverMauffret3,CatherineEtchebest1,BrigitteHartmann1,3* 1Dynamique des Structures et Interactions des Macromole′cules Biologiques, UMR 665 INSERM-Universite′ Paris Diderot, Sorbonne Paris Cite′, Institut National de la TransfusionSanguine,Paris,France,2LaboratoiredeBiochimieThe′orique,UPR9080CNRS,InstitutdeBiologiePhysico-Chimique,Paris,France,3LaboratoiredeBiologie etPharmacologieApplique′e,UMR8113CNRS-ENSdeCachan,Cachan,France Abstract ThisstudyinvestigatestheeffectofMg2+boundtotheDNAmajorgrooveonDNAstructureanddynamics.Theanalysisofa comprehensive dataset of B-DNA crystallographic structures shows that divalentcations are preferentially located in the DNAmajorgroovewheretheyinteractwithsuccessivebasesof(A/G)pGandthephosphategroupof59-CpAorTpG.Based 2+ onthisknowledge,moleculardynamicssimulationswerecarriedoutonaDNAoligomerwithoutorwithMg closetoan ApGstep.ThesesimulationsshowedthatthehydratedMg2+formsastableintra-strandcross-linkbetweenthetwopurines insolution.ApGgeneratesanelectrostaticpotentialinthemajorgroovethatisparticularlyattractiveforcations;itsintrinsic conformation is well-adapted to the formation of water-mediated hydrogen bonds with Mg . The binding of Mg 2+ 2+ modulates the behavior of the 59-neighboring step by increasing the BII (e-f.0u) population of its phosphate group. Additionalelectrostaticinteractionsbetweenthe59-phosphategroupandMg2+strengthenboththeDNA-cationbinding and the BII character of the 59-step. Cation binding in the major groove may therefore locally influence the DNA conformational landscape, suggesting a possible avenue for better understanding how strong DNA distortions can be stabilizedinprotein-DNAcomplexes. Citation:Gue′roultM,BoittinO,MauffretO,EtchebestC,HartmannB(2012)Mg2+intheMajorGrooveModulatesB-DNAStructureandDynamics.PLoSONE7(7): e41704.doi:10.1371/journal.pone.0041704 Editor:FrancaFraternali,King’sCollege,London,Unite