Department of Biosciences and Nutrition, Karolinska Institutet, NEO/Floor 8, Blickgången 16, 141 52, Huddinge, Sweden.
Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Riga, 1006, Latvia.
Sci Rep. 2020 Dec 10;10(1):21765. doi: 10.1038/s41598-020-78732-1.
Amyloid fibrils are mechanically robust and partly resistant to proteolytic degradation, making them potential candidates for scaffold materials in cell culture, tissue engineering, drug delivery and other applications. Such applications of amyloids would benefit from the possibility to functionalize the fibrils, for example by adding growth factors or cell attachment sites. The BRICHOS domain is found in a family of human proteins that harbor particularly amyloid-prone regions and can reduce aggregation as well as toxicity of several different amyloidogenic peptides. Recombinant human (rh) BRICHOS domains have been shown to bind to the surface of amyloid-β (Aβ) fibrils by immune electron microscopy. Here we produce fusion proteins between mCherry and rh Bri2 BRICHOS and show that they can bind to different amyloid fibrils with retained fluorescence of mCherry in vitro as well as in cultured cells. This suggests a "generic" ability of the BRICHOS domain to bind fibrillar surfaces that can be used to synthesize amyloid decorated with different protein functionalities.
淀粉样纤维具有很强的机械稳定性，并且部分抵抗蛋白水解降解，因此它们是细胞培养、组织工程、药物输送和其他应用中支架材料的潜在候选物。淀粉样蛋白的这些应用将受益于对纤维进行功能化的可能性，例如添加生长因子或细胞附着位点。BRICHOS 结构域存在于人类蛋白质家族中，该家族具有特别容易形成淀粉样蛋白的区域，并且可以减少几种不同的淀粉样肽的聚集和毒性。免疫电子显微镜显示，重组人（rh）BRICHOS 结构域能够与淀粉样-β（Aβ）纤维结合。在这里，我们在 mCherry 和 rh Bri2 BRICHOS 之间产生融合蛋白，并表明它们可以与不同的淀粉样纤维结合，在体外以及在培养的细胞中保持 mCherry 的荧光。这表明 BRICHOS 结构域具有结合纤维表面的“通用”能力，可用于合成具有不同蛋白质功能的淀粉样蛋白。
