Structural investigation of Rett-inducing MeCP2 mutations

作     者：Ottavia Spiga Simone Gardini Nicole Rossi Vittoria Cicaloni Francesco Pettini Neri Niccolai Annalisa Santucci 

作者机构：Department of BiotechnologyChemistry and PharmacyUniversity of SienaSiena53100Italy GenomeUp SRLRome00199Italy Toscana Life Sciences Foundation(TLS)Siena 53100Italy 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2019年第6卷第1期

页      面：31-34页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 081704[工学-应用化学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

主　　题：DNA binding domains MeCP2 Mutation distribution Protein structure Rett syndrome 

摘      要：X-ray structure of methyl-CpG binding domain(MBD)of MeCP2,an intrinsically disordered protein(IDP)involved in Rett syndrome,offers a rational basis for defining the spatial distribution for most of the sites where mutations responsible of Rett syndrome,RTT,*** have ascribed pathogenicity for mutations of amino acids bearing positively charged side chains,all located at the protein-DNA interface,as positive charge removal cause reduction of the MeCP2-DNA adduct *** of the frequent proline replacements,outside the DNA contact moiety of MBD,can be attributed to the role of this amino acid for maintaining both unfolded states for unbound MeCP2 and,at the same time,to favor some higher conformational order for stabilizing structural determinants required by protein *** hypotheses can be extended to transcription repressor domain,TRD,the other MeCP2-DNA interaction site and,in general,to all the IDP that interact with nucleic acids.