Intrinsically disordered proteins (IDPs) are challenging established structural biology perception and urge a reassessment of the conventional understanding of the subtle interplay between protein structure and dynamics. Due to their importance in eukaryotic life and central role in protein interaction networks, IDP research is a fascinating and highly relevant research area in which NMR spectroscopy is destined to be a key player. The flexible nature of IDPs, as a result of the sampling of a vast conformational space, however, poses a tremendous scientific challenge, both technically and theoretically. Pronounced signal averaging results in narrow signal dispersion and requires higher dimensionality NMR techniques. Moreover, a fundamental problem in the structural characterization of IDPs is the definition of the conformational ensemble sampled by the polypeptide chain in solution, where often the interpretation relies on the concept of 'residual structure' or 'conformational preference'. An important source of structural information is information-rich NMR experiments that probe protein backbone dihedral angles in a unique manner. Cross-correlated relaxation experiments have proven to fulfil this task as they provide unique information about protein backbones, particularly in IDPs. Here we present a novel cross-correlation experiment that utilizes non-uniform sampling detection schemes to resolve protein backbone dihedral ambiguities in IDPs. The sensitivity of this novel technique is illustrated with an application to the prototypical IDP [Formula: see text]-Synculein for which unexpected deviations from random-coil-like behaviour could be observed.

中文翻译：

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一种新颖的高维NMR实验，用于解决蛋白质骨架二面角的歧义。

本质上无序的蛋白质（IDP）挑战着已建立的结构生物学认识，并敦促重新评估对蛋白质结构与动力学之间的微妙相互作用的常规理解。由于它们在真核生物生命中的重要性以及在蛋白质相互作用网络中的核心作用，因此IDP研究是一个引人入胜且高度相关的研究领域，其中NMR光谱注定将成为关键参与者。然而，由于对巨大的构象空间进行采样，IDP的灵活性质在技术和理论上都构成了巨大的科学挑战。明显的信号平均会导致信号色散狭窄，并且需要更高维度的NMR技术。此外，IDP的结构表征中的一个基本问题是多肽链在溶液中采样的构象整体的定义，其中解释通常依赖于“残基结构”或“构象偏好”的概念。结构信息的重要来源是信息丰富的NMR实验，该实验以独特的方式探测蛋白质骨架的二面角。交叉相关的松弛实验已证明可以完成此任务，因为它们提供了有关蛋白质骨架的独特信息，尤其是在IDP中。在这里，我们提出了一种新颖的互相关实验，该实验利用非均匀采样检测方案来解决IDP中的蛋白质骨架二面体歧义。通过对原型IDP的应用说明了这种新技术的敏感性[公式：