2026-01-09 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/research_news/chem/202601/t20260108_1145477.shtml
- https://www.pnas.org/doi/10.1073/pnas.2515454123
生検で解像されたアミロイド線維のクライオ電子顕微鏡構造は、ALアミロイドーシスの分子生物学的知見を提供する Biopsy-resolved cryo-EM structures of amyloid fibrils provide molecular insights into AL amyloidosis
Yuxuan Yao, Qinyue Zhao, Shun Yao, +6 , and Dan Li
Proceedings of the National Academy of Sciences Published:January 6, 2026
DOI:https://doi.org/10.1073/pnas.2515454123
Significance
Determining amyloid fibril structures is essential for understanding disease mechanisms and guiding therapeutic development. However, most cryo-EM structures have been derived from postmortem tissues, leaving fibrils from living patients largely uncharacterized. Here, we present high-resolution structures of light chain (LC) amyloid fibrils extracted from cardiac and abdominal fat biopsies of three living patients with systemic light chain amyloidosis. We identify five distinct structures with patient- and tissue-specific features. Notably, fibrils from abdominal fat exhibit highly conserved global architectures compared to those from affected organs within the same patient. These findings offer insights into how LC sequence and tissue environment shape fibril conformation.
Abstract
Systemic light chain amyloidosis (AL) is characterized by amyloid fibril deposition in multiple organs, often severely affecting cardiac function. In this study, we extracted amyloid fibrils directly from abdominal fat and cardiac tissue biopsies obtained from three AL patients. Using cryo-electron microscopy, we determined five distinct structures of light chain (LC) amyloid fibrils. Our results demonstrate that LC fibrils from different patients adopt unique structural conformations, highlighting patient-specific fibril variations. Conversely, LC fibrils extracted from different tissues within the same patient share highly similar overall fibril structures, yet exhibit localized conformational variations, potentially shaped by distinct environmental cofactors. This study emphasizes the combined roles of patient-specific protein sequences and tissue-specific microenvironments in defining LC fibril conformation. The determination of LC fibril structures directly from easily accessible abdominal fat biopsy provides critical molecular insights into AL amyloidosis pathology, facilitating the development of therapeutic strategies.
