Jamal Salma, Kumari Anchala, Singh Aditi, Goyal Sukriti, Grover Abhinav
Department of Bioscience and Biotechnology, Banasthali University, Tonk, India.
Department of Biotechnology, TERI School of Advanced Studies, New Delhi, India.
Front Neurosci. 2017 Dec 7;11:684. doi: 10.3389/fnins.2017.00684. eCollection 2017.
Intrinsically disordered proteins (IDP) are a class of proteins that do not have a stable three-dimensional structure and can adopt a range of conformations playing various vital functional role. Alpha-synuclein is one such IDP which can aggregate into toxic protofibrils and has been associated largely with Parkinson's disease (PD) along with other neurodegenerative diseases. Osmolytes are small organic compounds that can alter the environment around the proteins by acting as denaturants or protectants for the proteins. In the present study, we have conducted a series of replica exchange molecular dynamics simulations to explore the role of osmolytes, urea which is a denaturant and TMAO (trimethylamine N-oxide), a protecting osmolyte, in aggregation and conformations of the synuclein peptide. We observed that both the osmolytes have significantly distinct impacts on the peptide and led to transitions of the conformations of the peptide from one state to other. Our findings highlighted that urea attenuated peptide aggregation and resulted in the formation of extended peptide structures whereas TMAO led to compact and folded forms of the peptide.
内在无序蛋白（IDP）是一类没有稳定三维结构的蛋白质，它们可以呈现多种构象并发挥各种重要的功能作用。α-突触核蛋白就是这样一种内在无序蛋白，它可以聚集成有毒的原纤维，并且在很大程度上与帕金森病（PD）以及其他神经退行性疾病相关。渗透溶质是小分子有机化合物，它们可以作为蛋白质的变性剂或保护剂来改变蛋白质周围的环境。在本研究中，我们进行了一系列副本交换分子动力学模拟，以探究渗透溶质、作为变性剂的尿素和作为保护性渗透溶质的三甲胺N-氧化物（TMAO）在突触核蛋白肽聚集和构象方面所起的作用。我们观察到这两种渗透溶质对该肽都有显著不同的影响，并导致肽的构象从一种状态转变为另一种状态。我们的研究结果表明，尿素减弱了肽的聚集并导致形成伸展的肽结构，而TMAO则导致肽形成紧凑和折叠的形式。
