Institute of Protein Biochemistry, Ulm University, Helmholtzstrasse 8/1, Ulm, D-89081, Germany.
Core Unit Mass Spectrometry and Proteomics, Medical Faculty, Ulm University, Ulm, D-89081, Germany.
Nat Commun. 2023 Nov 22;14(1):7623. doi: 10.1038/s41467-023-43301-3.
Systemic ATTR amyloidosis is an increasingly important protein misfolding disease that is provoked by the formation of amyloid fibrils from transthyretin protein. The pathological and clinical disease manifestations and the number of pathogenic mutational changes in transthyretin are highly diverse, raising the question whether the different mutations may lead to different fibril morphologies. Using cryo-electron microscopy, however, we show here that the fibril structure is remarkably similar in patients that are affected by different mutations. Our data suggest that the circumstances under which these fibrils are formed and deposited inside the body - and not only the fibril morphology - are crucial for defining the phenotypic variability in many patients.
系统性ATTR 淀粉样变是一种日益重要的蛋白质错误折叠疾病，由转甲状腺素蛋白形成淀粉样纤维引起。转甲状腺素蛋白的病理和临床疾病表现以及致病突变数量变化多样，这引发了一个问题，即不同的突变是否可能导致不同的纤维形态。然而，使用低温电子显微镜，我们在这里显示出，受不同突变影响的患者的纤维结构非常相似。我们的数据表明，这些纤维在体内形成和沉积的情况——而不仅仅是纤维形态——对于定义许多患者的表型变异性至关重要。
