Physical Chemistry I - Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn Street 4a, 44227 Dortmund, Germany.
Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-901, Brazil.
Biophys Chem. 2021 Jan;268:106506. doi: 10.1016/j.bpc.2020.106506. Epub 2020 Nov 14.
Our understanding of amyloid structures and the mechanisms by which disease-associated peptides and proteins self-assemble into these fibrillar aggregates, has advanced considerably in recent years. It is also established that amyloid fibrils are generally polymorphic. The molecular structures of the aggregation intermediates and the causes of molecular and structural polymorphism are less understood, however. Such information is mandatory to explain the pathological diversity of amyloid diseases. What is also clear is that not only protein mutations, but also the physiological milieu, i.e. pH, cosolutes, crowding and surface interactions, have an impact on fibril formation. In this minireview, we focus on the effect of the less explored physical parameters temperature and pressure on the fibrillization propensity of proteins and how these variables can be used to reveal additional mechanistic information about intermediate states of fibril formation and molecular and structural polymorphism. Generally, amyloids are very stable and can resist harsh environmental conditions, such as extreme pH, high temperature and high pressure, and can hence serve as valuable functional amyloid. As an example, we discuss the effect of temperature and pressure on the catalytic activity of peptide amyloid fibrils that exhibit enzymatic activity.
近年来，我们对淀粉样结构以及与疾病相关的肽和蛋白质如何自组装成这些纤维状聚集物的机制有了相当深入的了解。此外，已经确定淀粉样纤维通常是多态的。然而，对于聚集中间体的分子结构以及分子和结构多态性的原因了解较少。这种信息对于解释淀粉样疾病的病理多样性是必要的。显而易见的是，不仅蛋白质突变，而且生理环境，即 pH 值、共溶剂、拥挤和表面相互作用，都会影响纤维的形成。在这篇简评中，我们重点关注了研究较少的物理参数温度和压力对蛋白质纤维形成倾向的影响，以及这些变量如何用于揭示关于纤维形成的中间状态以及分子和结构多态性的额外机制信息。通常，淀粉样蛋白非常稳定，可以抵抗恶劣的环境条件，如极端 pH 值、高温和高压，因此可以作为有价值的功能性淀粉样蛋白。例如，我们讨论了温度和压力对表现出酶活性的肽淀粉样纤维的催化活性的影响。
