Systemic AL amyloidosis is a debilitating and potentially fatal disease that arises from the misfolding and fibrillation of immunoglobulin light chains (LCs). The disease is patient-specific with essentially each patient possessing a unique LC sequence. In this study, we present the first ex vivo fibril structures of a λ3 LC. The fibrils were extracted from the explanted heart of a patient (FOR005) and consist of 115 residues, mainly from the LC variable domain. The fibril structures imply that a 180° rotation around the disulfide bond and a major unfolding step are necessary for fibrils to form. The two fibril structures show highly similar fibril protein folds, differing in only a 12-residue segment. Remarkably, the two structures do not represent separate fibril morphologies, as they can co-exist at different z-axial positions within the same fibril. Our data imply the presence of structural breaks at the interface of the two structural forms.

中文翻译：

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Cryo-EM揭示了系统性AL淀粉样变性患者来源的淀粉样原纤维的结构断裂

系统性AL淀粉样变性病是一种由于免疫球蛋白轻链（LC）的错误折叠和原纤化而引起的衰弱性疾病，可能是致命性疾病。该疾病是患者特异性的，基本上每个患者都具有独特的LC序列。在这项研究中，我们介绍了λ3LC的第一个离体纤维结构。原纤维是从患者的离体心脏中提取的（FOR005），由115个残基组成，主要来自LC可变域。原纤维结构暗示了围绕原二硫键旋转180°和主要的展开步骤对于原纤维的形成是必需的。这两个原纤维结构显示出高度相似的原纤维蛋白折叠，仅在12个残基片段上不同。值得注意的是，这两个结构并不代表单独的原纤维形态，因为它们可以共存于同一原纤维的不同z轴位置。我们的数据暗示两种结构形式的界面处存在结构断裂。