Copper chaperone blocks amyloid formation via ternary complex.

IF 7.2 2区 生物学 Q1 BIOPHYSICS
Istvan Horvath, Tony Werner, Ranjeet Kumar, Pernilla Wittung-Stafshede
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引用次数: 8

Abstract

Protein misfolding in cells is avoided by a network of protein chaperones that detect misfolded or partially folded species. When proteins escape these control systems, misfolding may result in protein aggregation and amyloid formation. We here show that aggregation of the amyloidogenic protein α-synuclein (αS), the key player in Parkinson's disease, is controlled by the copper transport protein Atox1 in vitro. Copper ions are not freely available in the cellular environment, but when provided by Atox1, the resulting copper-dependent ternary complex blocks αS aggregation. Because the same inhibition was found for a truncated version of αS, lacking the C-terminal part, it appears that Atox1 interacts with the N-terminal copper site in αS. Metal-dependent chaperoning may be yet another manner in which cells control its proteome.

铜伴侣通过三元配合物阻断淀粉样蛋白的形成。
细胞中的蛋白质错误折叠是通过蛋白质伴侣蛋白网络来检测错误折叠或部分折叠的物种来避免的。当蛋白质脱离这些控制系统时,错误折叠可能导致蛋白质聚集和淀粉样蛋白形成。我们在这里发现淀粉样蛋白α-突触核蛋白(αS)的聚集是帕金森病的关键参与者,在体外由铜转运蛋白Atox1控制。铜离子在细胞环境中不是自由获得的,但当Atox1提供时,产生的依赖铜的三元配合物阻止αS聚集。由于缺少c末端部分的αS的截断版本发现了相同的抑制作用,因此似乎Atox1与αS的n末端铜位点相互作用。金属依赖性伴侣可能是细胞控制其蛋白质组的另一种方式。
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来源期刊
Quarterly Reviews of Biophysics
Quarterly Reviews of Biophysics 生物-生物物理
CiteScore
12.90
自引率
1.60%
发文量
16
期刊介绍: Quarterly Reviews of Biophysics covers the field of experimental and computational biophysics. Experimental biophysics span across different physics-based measurements such as optical microscopy, super-resolution imaging, electron microscopy, X-ray and neutron diffraction, spectroscopy, calorimetry, thermodynamics and their integrated uses. Computational biophysics includes theory, simulations, bioinformatics and system analysis. These biophysical methodologies are used to discover the structure, function and physiology of biological systems in varying complexities from cells, organelles, membranes, protein-nucleic acid complexes, molecular machines to molecules. The majority of reviews published are invited from authors who have made significant contributions to the field, who give critical, readable and sometimes controversial accounts of recent progress and problems in their specialty. The journal has long-standing, worldwide reputation, demonstrated by its high ranking in the ISI Science Citation Index, as a forum for general and specialized communication between biophysicists working in different areas. Thematic issues are occasionally published.
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