Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
Biochemistry. 2011 Dec 13;50(49):10567-9. doi: 10.1021/bi201578h. Epub 2011 Nov 17.
Pmel17 is a human amyloid involved in melanin synthesis. A fragment of Pmel17, the repeat domain (RPT) rich in glutamic acids, forms amyloid only at mildly acidic pH. Unlike pathological amyloids, these fibrils dissolve at neutral pH, supporting a reversible aggregation-disaggregation process. Here, we study RPT dissolution using atomic force microscopy and solution-state nuclear magnetic resonance spectroscopy. Our results reveal asymmetric fibril disassembly proceeding in the absence of intermediates. We suggest that fibril unfolding involves multiple deprotonation events resulting in electrostatic charge repulsion and filament dissolution.
Pmel17 是一种与人的黑色素合成有关的淀粉样蛋白。Pmel17 的一个片段，富含谷氨酸的重复结构域（RPT），仅在微酸性 pH 值下形成淀粉样纤维。与病理性淀粉样纤维不同，这些纤维在中性 pH 值下溶解，支持一个可逆的聚集-解聚过程。在这里，我们使用原子力显微镜和溶液态核磁共振波谱研究 RPT 的溶解。我们的结果揭示了不对称的纤维解聚过程，其中没有中间体的参与。我们提出纤维的展开涉及多个去质子化事件，导致静电排斥和纤维溶解。
