A new fibrillization mechanism of β-lactoglobulin in glycine solutions.
A new fibrillization mechanism of β-lactoglobulin in glycine solutions.
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DOI：
10.1016/j.ijbiomac.2022.06.182
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发表时间：
2022-09-01
影响因子：
8.2
通讯作者：
Hribar-Lee, Barbara
中科院分区：
文献类型：
--
作者：
Jaklin, Matej;Hritz, Jozef;Hribar-Lee, Barbara
尽管淀粉样蛋白聚集体在许多年前就被发现了，但其形成机制仍然是一个谜。由于它们与许多无法治疗的神经退行性疾病有关，因此寻找共同聚集途径的动机很高。我们报道了一种新的高热诱导的β-乳球蛋白（BLG）模型蛋白质在甘氨酸而不是水在pH 2孵育时的纤维化路径。通过结合原子力显微镜（AFM），透射发射显微镜（TEM），动态光散射（DLS）和圆二色性（CD），我们预测，在甘氨酸中制成的原纤维的基本构建块不是肽，而是通过堆叠环状结构形成的不同高度的球状体低聚物。球状低聚物通过打开和结合线性排列形成原纤维。我们推测甘氨酸是一种水解抑制剂，从而促进了不同的絮凝途径，结合已知的水中絮凝数据和我们的实验结论，我们提出了一种新的BLG絮凝方案。我们发现，通过改变过滤条件，只是通过缓冲液组成的微小变化可以显着改变聚集途径，缓冲液的影响不应被忽视。在我们的研究中看到的原纤维也得到越来越多的关注，因为它们的孔样结构和可能的细胞毒性机制，通过形成有害的离子通道。通过在一个简单的模型系统中制备它们作为BLG，我们开辟了一条新的途径来研究它们的形成。
Even though amyloid aggregates were discovered many years ago the mechanism of their formation is still a mystery. Because of their connection to many of untreatable neurodegenerative diseases the motivation for finding a common aggregation path is high. We report a new high heat induced fibrillization path of a model protein β-lactoglobulin (BLG) when incubated in glycine instead of water at pH 2. By combining atomic force microscopy (AFM), transmission emission microscopy (TEM), dynamic light scattering (DLS) and circular dichroism (CD) we predict that the basic building blocks of fibrils made in glycine are not peptides, but rather spheroid oligomers of different height that form by stacking of ring-like structures. Spheroid oligomers linearly align to form fibrils by opening up and combining. We suspect that glycine acts as an hydrolysation inhibitor which consequently promotes a different fibrillization path. By combining the known data on fibrillization in water with our experimental conclusions we come up with a new fibrillization scheme for BLG. We show that by changing the fibrillization conditions just by small changes in buffer composition can dramatically change the aggregation pathway and the effect of buffer shouldn’t be neglected. Fibrils seen in our study are also gaining more and more attention because of their pore-like structure and a possible cytotoxic mechanism by forming pernicious ion-channels. By preparing them in a simple model system as BLG we opened a new way to study their formation.
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