2024-07-16 スイス連邦工科大学ローザンヌ校(EPFL)
<関連情報>
- https://actu.epfl.ch/news/unraveling-amyloid-fibrils/
- https://onlinelibrary.wiley.com/doi/10.1002/advs.202402740
プロトフィラメントの階層的な絡み合いが混合曲率アミロイド多形の形成を支配する Hierarchical Protofilament Intertwining Rules the Formation of Mixed-Curvature Amyloid Polymorphs
Jiangtao Zhou, Salvatore Assenza, Meltem Tatli, Jiawen Tian, Ioana M. Ilie, Eugene L. Starostin, Amedeo Caflisch, Tuomas P. J. Knowles, Giovanni Dietler, Francesco S. Ruggeri …
Advanced Science Published: 20 June 2024
DOI:https://doi.org/10.1002/advs.202402740
Abstract
Amyloid polymorphism is a hallmark of almost all amyloid species, yet the mechanisms underlying the formation of amyloid polymorphs and their complex architectures remain elusive. Commonly, two main mesoscopic topologies are found in amyloid polymorphs characterized by non-zero Gaussian and mean curvatures: twisted ribbons and helical fibrils, respectively. Here, a rich heterogeneity of configurations is demonstrated on insulin amyloid fibrils, where protofilament packing can occur, besides the common polymorphs, also in a combined mode forming mixed-curvature polymorphs. Through AFM statistical analysis, an extended array of heterogeneous architectures that are rationalized by mesoscopic theoretical arguments are identified. Notably, an unusual fibrillization pathway is also unraveled toward mixed-curvature polymorphs via the widespread recruitment and intertwining of protofilaments and protofibrils. The results present an original view of amyloid polymorphism and advance the fundamental understanding of the fibrillization mechanism from single protofilaments into mature amyloid fibrils.
