Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871 (Japan).
Angew Chem Int Ed Engl. 2014 Jul 21;53(30):7799-804. doi: 10.1002/anie.201403815. Epub 2014 Jun 11.
Although amyloid fibrils are associated with numerous pathologies, their conformational stability remains largely unclear. Herein, we probe the thermal stability of various amyloid fibrils. α-Synuclein fibrils cold-denatured to monomers at 0-20 °C and heat-denatured at 60-110 °C. Meanwhile, the fibrils of β2-microglobulin, Alzheimer's Aβ1-40/Aβ1-42 peptides, and insulin exhibited only heat denaturation, although they showed a decrease in stability at low temperature. A comparison of structural parameters with positive enthalpy and heat capacity changes which showed opposite signs to protein folding suggested that the burial of charged residues in fibril cores contributed to the cold denaturation of α-synuclein fibrils. We propose that although cold-denaturation is common to both native proteins and misfolded fibrillar states, the main-chain dominated amyloid structures may explain amyloid-specific cold denaturation arising from the unfavorable burial of charged side-chains in fibril cores.
尽管淀粉样纤维与许多病理学有关，但它们的构象稳定性在很大程度上仍不清楚。在这里，我们探讨了各种淀粉样纤维的热稳定性。α-突触核蛋白纤维在 0-20°C 时冷变性为单体，在 60-110°C 时热变性。同时，β2-微球蛋白、阿尔茨海默病 Aβ1-40/Aβ1-42 肽和胰岛素的纤维仅表现出热变性，尽管它们在低温下稳定性降低。与正焓和热容变化的结构参数的比较表明，纤维核心中带电荷残基的埋藏有助于α-突触核蛋白纤维的冷变性。我们提出，尽管冷变性在天然蛋白质和错误折叠的纤维状态中都很常见，但主要链主导的淀粉样结构可能解释了由于纤维核心中带电荷侧链的不利埋藏而导致的淀粉样蛋白特异性冷变性。
