期刊
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
卷 16, 期 7, 页码 2989-3000出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3cp54383h
关键词
-
资金
- Andalusian Government [FQM-00123, FQM-02838]
- Spanish Ministry of Science and Innovation [BIO2009-07317]
- European Regional Development Fund of the European Union
Understanding the early molecular mechanisms governing amyloid aggregation is crucial to learn how to prevent it. Here, we used a site-directed mutagenesis approach to explore the molecular mechanism of nucleation of amyloid structure in the N47A Spc-SH3 domain. The changes in the native state stability produced by a series of mutations on each structural element of the domain were uncorrelated with the changes in the aggregation rates, although the overall aggregation mechanism was not altered. Analysis of the thioflavin T initial rates based on a simple kinetic model allowed us to extract thermodynamic magnitudes of the precursor states of nucleation and map the regions of the protein participating in the structure of the amyloidogenic precursors. This structure differs from that of the folding transition state of the SH3 domains, strongly suggesting that the regions of the conformational landscape leading to amyloid formation are divergent from those leading to the native fold.
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