Revisit the effect of fibrillization on functions of prion protein from the perspective of Cu(II) binding.
Revisit the effect of fibrillization on functions of prion protein from the perspective of Cu(II) binding.
复制标题
从 Cu(II) 结合的角度重新审视纤维化对朊病毒蛋白功能的影响。
DOI：
10.1016/j.bbrc.2018.05.118
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发表时间：
2018
影响因子：
3.1
通讯作者：
McGuirl,Michele
中科院分区：
文献类型：
--
作者：
Qi,Xu;McGuirl,Michele
朊蛋白（PrP）由α-螺旋结构向β-折叠结构的转变是朊病毒病病因学的关键事件。大量证据表明PrP的生理功能与其与Cu（II）的结合能力有关，提示PrP可能是铜离子的缓冲剂或铜离子转运系统的一部分。相比之下，很少有人关注铜（II）结合羊瘙痒症的形式。本工作的目标是比较研究在不同的pH值下，使用连续的X-波段电子顺磁共振（EPR）光谱PrP构象之间的配位几何形状。我们已经发现，虽然PrP的α-螺旋单体和纤维形式与Cu（II）的结合相似，但多His构型在纤维形式中更有利。我们的结果为纤维化对朊病毒蛋白功能的影响提供了见解。
Conversion of prion protein (PrP) from its α-helical form to a β-sheet rich scrapie form constitutes the key event of the etiology of prion diseases. Fundamental questions remain concerning the functions of prion protein and the mechanisms leading to the formation of misfolded forms.A wealth of evidence links physiological functions of PrP to its ability to bind Cu(II), suggesting that it may act as a copper buffer or be part of the copper transportation system. In contrast, much less attention has been devoted to understanding Cu(II) binding to the scrapie forms. The goal of this work is to comparatively investigate the coordination geometries among PrP conformers at different pH values using continuous X-band electron paramagnetic resonance (EPR) spectroscopy. We have found that while both α-helical monomeric and fibrillar forms of PrP bind Cu(II) similarly, the multi-His configuration is more favored in the fibrillar form. Our results have provided insights into the effect of fibrillization on the functions of prion protein.