Department of Health Sciences & Technology, ETH Zurich, Schmelzbergstrasse 9, 8092, Zurich, Switzerland.
Department of Materials, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland.
Angew Chem Int Ed Engl. 2018 Jul 9;57(28):8370-8382. doi: 10.1002/anie.201713416. Epub 2018 Jun 8.
Protein folding involves a large number of steps and conformations in which the folding protein samples different thermodynamic states characterized by local minima. Kinetically trapped on- or off-pathway intermediates are metastable folding intermediates towards the lowest absolute energy minima, which have been postulated to be the natively folded state where intramolecular interactions dominate, and the amyloid state where intermolecular interactions dominate. However, this view largely neglects the rich polymorphism found within amyloid species. We review the protein folding energy landscape in view of recent findings identifying specific transition routes among different amyloid polymorphs. Observed transitions such as twisted ribbon→crystal or helical ribbon→nanotube, and forbidden transitions such helical ribbon↛crystal, are discussed and positioned within the protein folding and aggregation energy landscape. Finally, amyloid crystals are identified as the ground state of the protein folding and aggregation energy landscape.
蛋白质折叠涉及大量步骤和构象，其中折叠蛋白质会经历不同的热力学状态，这些状态由局部最小值来描述。在或不在途径上被动力学捕获的中间态是朝着绝对最低能量最小值的亚稳态折叠中间态，这些中间态被假设为是天然折叠状态，其中分子内相互作用占主导地位，以及淀粉样状态，其中分子间相互作用占主导地位。然而，这种观点在很大程度上忽略了淀粉样物种中发现的丰富的多态性。我们回顾了蛋白质折叠能量景观，鉴于最近的发现，确定了不同淀粉样多态体之间的特定转变途径。讨论了观察到的转变，如扭曲的带状物→晶体或螺旋带状物→纳米管，以及禁止的转变，如螺旋带状物↛晶体，并将其置于蛋白质折叠和聚集能量景观内。最后，淀粉样晶体被确定为蛋白质折叠和聚集能量景观的基态。
