000061697 001__ 61697
000061697 005__ 20190709135443.0
000061697 0247_ $$2doi$$a10.1038/srep41635
000061697 0248_ $$2sideral$$a99151
000061697 037__ $$aART-2017-99151
000061697 041__ $$aeng
000061697 100__ $$aClaveria-Gimeno, R.
000061697 245__ $$aThe intervening domain from MeCP2 enhances the DNA affinity of the methyl binding domain and provides an independent DNA interaction site
000061697 260__ $$c2017
000061697 5060_ $$aAccess copy available to the general public$$fUnrestricted
000061697 5203_ $$aMethyl-CpG binding protein 2 (MeCP2) preferentially interacts with methylated DNA and it is involved in epigenetic regulation and chromatin remodelling. Mutations in MeCP2 are linked to Rett syndrome, the leading cause of intellectual retardation in girls and causing mental, motor and growth impairment. Unstructured regions in MeCP2 provide the plasticity for establishing interactions with multiple binding partners. We present a biophysical characterization of the methyl binding domain (MBD) from MeCP2 reporting the contribution of flanking domains to its structural stability and dsDNA interaction. The flanking disordered intervening domain (ID) increased the structural stability of MBD, modified its dsDNA binding profile from an entropically-driven moderate-affinity binding to an overwhelmingly enthalpically-driven high-affinity binding. Additionally, ID provided an additional site for simultaneously and autonomously binding an independent dsDNA molecule, which is a key feature linked to the chromatin remodelling and looping activity of MeCP2, as well as its ability to interact with nucleosomes replacing histone H1. The dsDNA interaction is characterized by an unusually large heat capacity linked to a cluster of water molecules trapped within the binding interface. The dynamics of disordered regions together with extrinsic factors are key determinants of MeCP2 global structural properties and functional capabilities.
000061697 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B01$$9info:eu-repo/grantAgreement/ES/DGA/B136-13$$9info:eu-repo/grantAgreement/ES/DGA/B89$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00663$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-0017$$9info:eu-repo/grantAgreement/ES/MEC/FPU13-3870$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P
000061697 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000061697 590__ $$a4.122$$b2017
000061697 591__ $$aMULTIDISCIPLINARY SCIENCES$$b12 / 64 = 0.188$$c2017$$dQ1$$eT1
000061697 592__ $$a1.533$$b2017
000061697 593__ $$aMultidisciplinary$$c2017$$dQ1
000061697 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000061697 700__ $$0(orcid)0000-0001-7328-2094$$aLanuza, P.M.$$uUniversidad de Zaragoza
000061697 700__ $$aMorales-Chueca, I.
000061697 700__ $$aJorge-Torres, O.C.
000061697 700__ $$0(orcid)0000-0002-1232-6310$$aVega, S.
000061697 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, O.$$uUniversidad de Zaragoza
000061697 700__ $$aEsteller, M.
000061697 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000061697 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000061697 773__ $$g7 (2017), 41635$$pSci. rep.$$tScientific reports$$x2045-2322
000061697 8564_ $$s1333357$$uhttps://zaguan.unizar.es/record/61697/files/texto_completo.pdf$$yVersión publicada
000061697 8564_ $$s110632$$uhttps://zaguan.unizar.es/record/61697/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000061697 909CO $$ooai:zaguan.unizar.es:61697$$particulos$$pdriver
000061697 951__ $$a2019-07-09-11:37:10
000061697 980__ $$aARTICLE