期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12563
关键词
-
资金
- Parkinson's UK [H-1103]
- Wellcome Trust [104933/Z/14/Z, 089703/Z/09/Z]
- UK Medical Research Council [MR/N000676/1, MR/K015850/1, MR/K02292X/1]
- UK Engineering and Physical Sciences Research Council [EP/H018301/1]
- EPSRC [EP/H018301/1, EP/K039520/1] Funding Source: UKRI
- MRC [MC_G1000734, MR/N012453/1, MR/K015850/1, MR/K02292X/1, MR/N000676/1] Funding Source: UKRI
- Wellcome Trust [104933/Z/14/Z] Funding Source: Wellcome Trust
- Alzheimers Research UK [ARUK-PG2013-14, ARUK-EG2012A-1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/K039520/1, EP/H018301/1, 1362139] Funding Source: researchfish
- Medical Research Council [MR/N000676/1, MR/K02292X/1, MR/N012453/1, MR/K015850/1, MC_G1000734] Funding Source: researchfish
- Parkinson's UK [H-1103] Funding Source: researchfish
alpha-synuclein (alpha S) is an intrinsically disordered protein whose fibrillar aggregates are the major constituents of Lewy bodies in Parkinson's disease. Although the specific function of alpha S is still unclear, a general consensus is forming that it has a key role in regulating the process of neurotransmitter release, which is associated with the mediation of synaptic vesicle interactions and assembly. Here we report the analysis of wild-type alpha S and two mutational variants linked to familial Parkinson's disease to describe the structural basis of a molecular mechanism enabling alpha S to induce the clustering of synaptic vesicles. We provide support for this 'double-anchor' mechanism by rationally designing and experimentally testing a further mutational variant of alpha S engineered to promote stronger interactions between synaptic vesicles. Our results characterize the nature of the active conformations of alpha S that mediate the clustering of synaptic vesicles, and indicate their relevance in both functional and pathological contexts.
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