Institute of Protein Biochemistry, Ulm University, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Center for Integrated Protein Science Munich (CIPSM), Technische Universität München, Department Chemie, 85748, Garching, Germany.
Angew Chem Int Ed Engl. 2017 Jun 19;56(26):7510-7514. doi: 10.1002/anie.201701761. Epub 2017 May 23.
Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post-translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril. Our data imply for both analyzed forms of amyloidosis that the pathways of protein misfolding are systemically conserved; that is, they follow the same rules irrespective of where inside one body fibrils are formed or accumulated.
系统性淀粉样变性是由循环淀粉样前体蛋白错误折叠和淀粉样纤维在多个器官中的沉积引起的。对来自人类 AL 和鼠 AA 淀粉样变性的淀粉样纤维进行化学和生物物理分析，揭示了同一患者或患病动物不同组织或器官中相同的纤维形态。观察到的结构相似性涉及纤维形态、纤维蛋白的一级和二级结构、存在的翻译后修饰，以及在 AL 纤维的情况下，纤维内多肽链的部分折叠特征。我们的数据表明，对于分析的两种淀粉样变性形式，蛋白质错误折叠的途径在系统上是保守的；也就是说，无论纤维在体内何处形成或积累，它们都遵循相同的规则。
