期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 139, 期 16, 页码 5640-5643出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.6b11039
关键词
-
资金
- Boehringer-Ingelheim Foundation
- German Research Foundation (DFG) via the Collaborative Research Center [SFB 1093]
- German Research Foundation (DFG) via the Excellence Cluster RESOLV [EXC1069]
- Berlin Institute of Health for Collaborative Research Grant of the German Federal Ministry for Education and Research (BMBF) [1.1.2.a.3]
- Helmholtz Validation Fund [HVF-0013]
- U.S. National Institutes of Health [R01GM103479, S10RR028893]
- U.S. Department of Energy (UCLA/DOE Institute of Genomics and Proteomics) [DE-FC03-02ER63421]
Huntington's disease is a neurodegenerative disorder associated with the expansion of the polyglutamine tract in the exon-1 domain of the huntingtin protein (htt(el)). Above a threshold of 37 glutamine residues, httel starts to aggregate in a nucleation-dependent manner. A 17-residue N-terminal fragment of htt(el) (N17) has been suggested to play a crucial role in modulating the aggregation propensity and toxicity of htt(el). Here we identify N17 as a potential target for novel therapeutic intervention using the molecular tweezer CLR01. A combination of biochemical experiments and computer simulations shows that binding of CLR01 induces structural rearrangements within the htt(el) monomer and inhibits htt(el) aggregation, underpinning the key role of N17 in modulating htt(el) toxicity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据