The aggregation of antibody light chains is linked to systemic light chain (AL) amyloidosis, a disease where amyloid deposits frequently affect the heart and the kidney. We here investigate fibrils from the λ-III FOR005 light chain (LC), which is derived from an AL-patient with severe cardiac involvement. In FOR005, five residues are mutated with respect to its closest germline gene segment IGLV3-19 and IGLJ3. All mutations are located close to the complementarity determining regions (CDRs). The sequence segments responsible for the fibril formation are not yet known. We use fibrils extracted from the heart of this particular amyloidosis patient as seeds to prepare fibrils for solid-state NMR. We show that the seeds induce the formation of a specific fibril structure from the biochemically produced protein. We have assigned the fibril core region of the FOR005-derived fibrils and characterized the secondary structure propensity of the observed amino acids. As the primary structure of the aggregated patient protein is different for every AL patient, it is important to study, analyze and report a greater number of light chain sequences associated with AL amyloidosis.

抗体轻链的聚集与系统性轻链 (AL) 淀粉样变性有关，这是一种淀粉样蛋白沉积经常影响心脏和肾脏的疾病。我们在此研究来自 λ-III FOR005 轻链 (LC) 的原纤维，该轻链源自患有严重心脏受累的 AL 患者。在FOR005中，相对于其最接近的种系基因片段IGLV3-19和IGLJ3，五个残基发生突变。所有突变都位于互补决定区 (CDR) 附近。负责原纤维形成的序列片段尚不清楚。我们使用从该特殊淀粉样变性患者的心脏中提取的原纤维作为种子来制备用于固态核磁共振的原纤维。我们发现种子诱导生化产生的蛋白质形成特定的原纤维结构。我们已经指定了 FOR005 衍生原纤维的原纤维核心区域，并表征了观察到的氨基酸的二级结构倾向。由于每个 AL 患者聚集的患者蛋白的一级结构都不同，因此研究、分析和报告大量与 AL 淀粉样变性相关的轻链序列非常重要。