Rationally Designed Variants of α-Synuclein Illuminate Its in vivo Structural Properties in Health and Disease.
Rationally Designed Variants of α-Synuclein Illuminate Its in vivo Structural Properties in Health and Disease.
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DOI：
10.3389/fnins.2018.00623
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发表时间：
2018
影响因子：
4.3
通讯作者：
Dettmer U
中科院分区：
文献类型：
--
作者：
Dettmer U
α-突触核蛋白（α-Synuclein，αS）是一种保守的神经元蛋白，具有独特的结构特征。它似乎在折叠状态和非结构化状态之间以及在膜结合状态和水溶性状态之间分配。此外，最近已经观察到单体和四聚体/多聚体状态之间的切换。多聚体种类的精确组成、定位和丰度正在研究中，并且仍然不确定。然而，为了干预疾病的发病机制，我们必须剖析αS稳态的微小变化如何引起帕金森病（PD）、路易体痴呆（DLB）和其他人类突触核蛋白病。合理设计的αS点突变，防止蛋白质在其正常折叠库中占据所有状态，继续有助于对其体内生物化学带来新的见解。本文综述了不同实验室关于αS稳态的生化和细胞生物学研究结果，特别强调了可能保留αS复杂亚稳态天然状态的完整细胞方法。
α-Synuclein (αS) is a conserved and abundant neuronal protein with unusual structural properties. It appears to partition between folded and unstructured states as well as between membrane-bound and aqueously soluble states. In addition, a switch between monomeric and tetrameric/multimeric states has been observed recently. The precise composition, localization and abundance of the multimeric species are under study and remain unsettled. Yet to interfere with disease pathogenesis, we must dissect how small changes in αS homeostasis may give rise to Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and other human synucleinopathies. Rationally designed αS point mutations that prevent the protein from populating all states within its normal folding repertoire have continued to be instrumental in bringing new insights into its biochemistry in vivo. This review summarizes biochemical and cell biological findings about αS homeostasis from different labs, with a special emphasis on intact-cell approaches that may preserve the complex, metastable native states of αS.
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影响因子：
8.6
作者：
Appel-Cresswell, Silke;Vilarino-Guell, Carles;Farrer, Matthew J.
通讯作者：
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DOI：
10.1073/pnas.0407146102
发表时间：
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