Intrinsically disordered proteins (IDPs) regularly constitute components of larger protein assemblies contributing to architectural stability. Two small, highly acidic IDPs have been linked to the so-called PCI complexes carrying PCI-domain subunits, including the proteasome lid and the COP9 signalosome. These two IDPs, DSS1 and CSNAP, have been proposed to have similar structural propensities and functions, but they display differences in their interactions and interactome sizes. Here we characterized the structural properties of human DSS1 and CSNAP at the residue level using NMR spectroscopy and probed their propensities to bind ubiquitin. We find that distinct structural features present in DSS1 are completely absent in CSNAP, and vice versa, with lack of relevant ubiquitin binding to CSNAP, suggesting the two proteins to have diverged in both structure and function. Our work additionally highlights that different local features of seemingly similar IDPs, even subtle sequence variance, may endow them with different functional traits. Such traits may underlie their potential to engage in multiple interactions thereby impacting their interactome sizes.

中文翻译：

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无序的 PCI 结合人类蛋白 CSNAP 和 DSS1 在结构和功能上存在分歧

固有无序蛋白质 (IDP) 定期构成有助于结构稳定性的较大蛋白质组件的组成部分。两个小的、高酸性的 IDP 与携带 PCI 域亚基的所谓 PCI 复合物有关，包括蛋白酶体盖和 COP9 信号小体。这两个 IDP，DSS1 和 CSNAP，已被提议具有相似的结构倾向和功能，但它们在相互作用和相互作用组大小方面表现出差异。在这里，我们使用核磁共振光谱在残留水平上表征了人类 DSS1 和 CSNAP 的结构特性，并探讨了它们结合泛素的倾向。我们发现 DSS1 中存在的独特结构特征在 CSNAP 中完全不存在，反之亦然，缺乏与 CSNAP 相关的泛素结合，表明这两种蛋白质在结构和功能上都存在分歧。我们的工作还强调了看似相似的 IDP 的不同局部特征，即使是细微的序列差异，也可能赋予它们不同的功能特征。这些特征可能是它们参与多种交互的潜力的基础，从而影响它们的交互组大小。