Institute of Protein Biochemistry, Ulm University, Ulm, Germany.
Medicinal Department V, Amyloidosis Centre, Heidelberg University Hospital, Heidelberg, Germany.
Nat Commun. 2024 Jun 15;15(1):5121. doi: 10.1038/s41467-024-49520-6.
Systemic AL amyloidosis is one of the most frequently diagnosed forms of systemic amyloidosis. It arises from mutational changes in immunoglobulin light chains. To explore whether these mutations may affect the structure of the formed fibrils, we determine and compare the fibril structures from several patients with cardiac AL amyloidosis. All patients are affected by light chains that contain an IGLV3-19 gene segment, and the deposited fibrils differ by the mutations within this common germ line background. Using cryo-electron microscopy, we here find different fibril structures in each patient. These data establish that the mutations of amyloidogenic light chains contribute to defining the fibril architecture and hence the structure of the pathogenic agent.
系统性 AL 淀粉样变性是最常见的系统性淀粉样变性形式之一。它源于免疫球蛋白轻链的突变。为了探究这些突变是否会影响形成的纤维的结构，我们对几位患有心脏 AL 淀粉样变性的患者的纤维结构进行了测定和比较。所有患者受含有 IGLV3-19 基因片段的轻链影响，而沉积的纤维在该常见的胚系背景内的突变上有所不同。使用低温电子显微镜，我们在此发现每位患者的纤维结构均不同。这些数据表明，淀粉样变性轻链的突变有助于确定纤维的结构，从而确定致病剂的结构。
