Structural Ensembles of Membrane-bound α-Synuclein Reveal the Molecular Determinants of Synaptic Vesicle Affinity.
Structural Ensembles of Membrane-bound α-Synuclein Reveal the Molecular Determinants of Synaptic Vesicle Affinity.
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DOI：
10.1038/srep27125
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发表时间：
2016-06-08
影响因子：
4.6
通讯作者：
Dobson CM
中科院分区：
文献类型：
--
作者：
Fusco G;De Simone A;Arosio P;Vendruscolo M;Veglia G;Dobson CM
α-突触核蛋白(αS)是一种140个残基的蛋白质，其聚集与帕金森病有关，详细表征其膜结合的分子决定因素对于阐明该蛋白质功能和功能失调过程之间的平衡调节方式具有基础性意义。尽管具有生物学意义，但膜结合状态αS的结构性质仍然难以捉摸，部分原因是该蛋白质固有的动态性质，也因为在生理相关的环境中研究这种状态存在困难。在本研究中，我们使用了固体核磁共振和限制性MD模拟来精炼αS与突触样膜表面结合的N端区域的结构和拓扑。这个区域在αS的结合机制中具有基本的重要性，因为它起到将蛋白质锚定到脂质双层上的作用。这一结果为确定影响αS膜结合态生物学特性的关键因素奠定了基础。
A detailed characterisation of the molecular determinants of membrane binding by α-synuclein (αS), a 140-residue protein whose aggregation is associated with Parkinson’s disease, is of fundamental significance to clarify the manner in which the balance between functional and dysfunctional processes are regulated for this protein. Despite its biological relevance, the structural nature of the membrane-bound state αS remains elusive, in part because of the intrinsically dynamic nature of the protein and also because of the difficulties in studying this state in a physiologically relevant environment. In the present study we have used solid-state NMR and restrained MD simulations to refine structure and topology of the N-terminal region of αS bound to the surface of synaptic-like membranes. This region has fundamental importance in the binding mechanism of αS as it acts as to anchor the protein to lipid bilayers. The results enabled the identification of the key elements for the biological properties of αS in its membrane-bound state.