Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 1 Pasteur Street, 02-093 Warsaw, Poland.
Institute of High Pressure Physics, Polish Academy of Sciences, 29/37 Sokołowska Street, 01-142 Warsaw, Poland.
J Mater Chem B. 2021 Oct 27;9(41):8626-8630. doi: 10.1039/d1tb01976g.
ATP acts as a biological hydrotrope preventing protein aggregation. Here, we report a novel chimeric peptide, ACCK, with an unusual capacity to bind and incorporate ATP while self-assembling into amyloid fibrils. The amino acid sequence combines a highly amyloidogenic segment of insulin's A-chain (ACC) and octalysine (K). Fibrillization requires binding 2 ATP molecules per ACCK monomer and is not triggered by adenosine di- and monophosphates (ADP, AMP). Infrared and CD spectra and AFM-based morphological analysis reveal tight and orderly entrapment of ATP within superstructural hybrid peptide-ATP fibrils. The incorporation of ATP is an emergent property of ACCK not observed for ACC and K segments separately. We demonstrate how new functionalities ( ATP storage) emerge from synergistic coupling of amyloidogenic segments with non-amyloidogenic peptide ligands, and suggest that ATP's role in protein misfolding is more nuanced than previously assumed.
ATP 作为一种生物增溶剂，可防止蛋白质聚集。在这里，我们报告了一种新型嵌合肽 ACCK，它具有结合和掺入 ATP 的独特能力，同时自组装成淀粉样纤维。该氨基酸序列结合了胰岛素 A 链（ACC）和八赖氨酸（K）的高度淀粉样片段。纤维形成需要每个 ACCK 单体结合 2 个 ATP 分子，并且不受腺嘌呤二磷酸和一磷酸（ADP、AMP）的触发。红外和 CD 光谱以及基于原子力显微镜的形态分析揭示了 ATP 在超结构混合肽-ATP 纤维内的紧密有序捕获。对于 ACC 和 K 片段单独而言，ATP 的掺入不是 ACCK 观察到的涌现特性。我们展示了如何通过将淀粉样片段与非淀粉样肽配体协同耦合来产生新的功能（ATP 存储），并表明 ATP 在蛋白质错误折叠中的作用比以前假设的更为复杂。
