Poly(ADP-ribose) (PAR), a non-canonical nucleic acid, is essential for DNA/RNA metabolism and protein condensation, and its dysregulation is linked to cancer and neurodegeneration. However, key structural insights into PAR’s functions remain largely uncharacterized, hindered by the challenges in synthesizing and characterizing PAR, which are attributed to its length heterogeneity. A central issue is how PAR, comprised solely of ADP-ribose units, attains specificity in its binding and condensing proteins based on chain length. Here, we integrate molecular dynamics simulations with small-angle X-ray scattering to analyze PAR structures. We identify diverse structural ensembles of PAR that fall into distinct subclasses and reveal distinct compaction of two different lengths of PAR upon the addition of small amounts of Mg²⁺ ions. Unlike PAR₁₅, PAR₂₂ forms ADP-ribose bundles via local intramolecular coil-to-globule transitions. Understanding these length-dependent structural changes could be central to deciphering the specific biological functions of PAR.

聚 （ADP-核糖） （PAR） 是一种非经典核酸，对 DNA/RNA 代谢和蛋白质浓缩至关重要，其失调与癌症和神经退行性变有关。然而，对 PAR 功能的关键结构见解在很大程度上仍未得到表征，这受到合成和表征 PAR 挑战的阻碍，这归因于其长度异质性。一个核心问题是仅由 ADP-核糖单元组成的 PAR 如何在其结合和凝聚蛋白中根据链长获得特异性。在这里，我们将分子动力学模拟与小角 X 射线散射相结合，以分析 PAR 结构。我们确定了属于不同亚类的 PAR 的不同结构集合，并揭示了在添加少量 Mg²⁺ 离子时两种不同长度的 PAR 的不同压缩。与 PAR₁₅ 不同，PAR₂₂ 通过局部分子内线圈到小球转变形成 ADP-核糖束。了解这些长度依赖性结构变化可能是破译 PAR 特定生物学功能的核心。