Structural investigation of Rett-inducing MeCP2 mutations  

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

机构地区：[1]Department of Biotechnology,Chemistry and Pharmacy,University of Siena,Siena,53100,Italy [2]GenomeUp SRL,Rome,00199,Italy [3]Toscana Life Sciences Foundation(TLS),Siena 53100,Italy

出　　处：《Genes & Diseases》2019年第1期31-34,共4页基因与疾病（英文）

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,occur.We 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 lifetime.Pathogenicity 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 activity.These 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.

关 键 词：DNA binding domains MECP2 Mutation distribution Protein structure Rett syndrome 

分 类 号：O62[理学—有机化学]