Pauwels Kris, Lebrun Pierre, Tompa Peter
VIB-VUB Center for Structural Biology (CSB), Vlaams Instituut voor Biotechnologie (VIB), Brussels, Belgium.
Structural Biology Brussels (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Cell Mol Life Sci. 2017 Sep;74(17):3185-3204. doi: 10.1007/s00018-017-2561-6. Epub 2017 Jun 13.
There is ample evidence that many proteins or regions of proteins lack a well-defined folded structure under native-like conditions. These are called intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs). Whether this intrinsic disorder is also their main structural characteristic in living cells has been a matter of intense debate. The structural analysis of IDPs became an important challenge also because of their involvement in a plethora of human diseases, which made IDPs attractive targets for therapeutic development. Therefore, biophysical approaches are increasingly being employed to probe the structural and dynamical state of proteins, not only in isolation in a test tube, but also in a complex biological environment and even within intact cells. Here, we survey direct and indirect evidence that structural disorder is in fact the physiological state of many proteins in the proteome. The paradigmatic case of α-synuclein is used to illustrate the controversial nature of this topic.
有充分证据表明，许多蛋白质或蛋白质区域在类天然条件下缺乏明确的折叠结构。这些被称为内在无序蛋白质（IDP）或内在无序区域（IDR）。这种内在无序是否也是它们在活细胞中的主要结构特征一直是激烈争论的话题。IDP的结构分析也成为一项重要挑战，因为它们与众多人类疾病有关，这使得IDP成为治疗开发的有吸引力的靶点。因此，生物物理方法越来越多地被用于探究蛋白质的结构和动态状态，不仅是在试管中单独研究，还包括在复杂的生物环境中甚至完整细胞内。在这里，我们审视直接和间接证据，以证明结构无序实际上是蛋白质组中许多蛋白质的生理状态。α-突触核蛋白的典型案例被用来说明这个话题的争议性。
