Institut für Physiologische Chemie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Hollystr. 1, D-06114 Halle/Saale, Germany.
Biol Chem. 2019 Jun 26;400(7):895-915. doi: 10.1515/hsz-2018-0458.
Protein folding is one of the fundamental processes in life and therefore needs to be tightly regulated. Many cellular quality control systems are in place to ensure that proteostasis is optimally adjusted for a changing environment, facilitating protein folding, translocation and degradation. These systems include the molecular chaperones and the major protein degradation systems, namely the ubiquitin proteasome system and autophagy. However, the capacity of the quality control systems can be exhausted and protein misfolding and aggregation, including the formation of amyloids, can occur as a result of ageing, mutations or exogenous influences. There are many known diseases in which protein misfolding and aggregation can be the underlying cause of the pathological condition; these are referred to as proteinopathies. Over the last decade, it has become clear that posttranslational modifications can govern and modulate protein folding, and that aberrant posttranslational modifications can cause or contribute to proteinopathies. This review provides an overview of protein folding and misfolding and the role of the major protein quality control systems. It focusses on different posttranslational modifications and gives examples of how these posttranslational modifications can alter protein folding and cause or accompany proteinopathies.
蛋白质折叠是生命中的基本过程之一，因此需要受到严格调控。许多细胞质量控制系统已经就位，以确保蛋白质稳态能够根据不断变化的环境进行最佳调整，促进蛋白质折叠、转运和降解。这些系统包括分子伴侣以及主要的蛋白质降解系统，即泛素蛋白酶体系统和自噬。然而，质量控制系统的能力可能会耗尽，蛋白质错误折叠和聚集，包括淀粉样蛋白的形成，可能会由于衰老、突变或外源性影响而发生。有许多已知疾病中，蛋白质错误折叠和聚集可能是病理状况的根本原因；这些疾病被称为蛋白质病。在过去十年中，已经清楚地认识到翻译后修饰可以控制和调节蛋白质折叠，并且异常的翻译后修饰可以导致或促成蛋白质病。本综述概述了蛋白质折叠和错误折叠以及主要蛋白质质量控制系统的作用。它聚焦于不同的翻译后修饰，并举例说明这些翻译后修饰如何改变蛋白质折叠并导致或伴随蛋白质病。
