Department of Inorganic Chemistry , University of Granada , 18071 Granada , Spain.
Department of Health Sciences and Technology , ETH Zürich , 8092 Zürich , Switzerland.
J Am Chem Soc. 2019 Jan 30;141(4):1606-1613. doi: 10.1021/jacs.8b11418. Epub 2019 Jan 14.
Ferritin, a soluble and highly robust protein with subunits packed into well-defined helices, is a key component of the iron regulatory system in the brain and thus is widely recognized as a crucial protein for iron metabolism, but may also bear possible implications in some neurodegenerative disorders. Here, we present evidence of how human recombinant apoferritin can convert into an unusual structure from its folded native state; that is, amyloid fibrils analogue to those found in pathological disorders such as Alzheimer's and Parkinson's diseases. An extensive combination of advanced microscopy, spectroscopy and scattering techniques concur to reveal that apoferritin fibrils possess a common double stranded twisted ribbon structure which can result in a mesoscopic right-handed chirality. We highlight a direct connection between the chirality and morphology of the resulting amyloid fibrils, and the initial protein subunits composition, advancing our understanding on the possible role of misfolding in some ferritin-related pathologies and posing new bases for the design of chiral 1D functional nanostructures.
铁蛋白是一种可溶性且高度稳定的蛋白，其亚基组装成明确的螺旋，是大脑中铁调节系统的关键组成部分，因此被广泛认为是铁代谢的关键蛋白，但也可能与一些神经退行性疾病有关。在这里，我们提供了证据表明人重组脱铁铁蛋白如何从其折叠的天然状态转变为一种不寻常的结构；即类似于阿尔茨海默病和帕金森病等病理疾病中发现的淀粉样纤维。广泛结合先进的显微镜、光谱和散射技术证实，脱铁铁蛋白纤维具有常见的双链扭曲带状结构，可导致介观右手手性。我们强调了手性和形态之间的直接联系，以及由此产生的淀粉样纤维的初始蛋白质亚基组成，这推进了我们对一些铁蛋白相关病理学中错误折叠可能作用的理解，并为设计手性 1D 功能纳米结构提供了新的基础。
