TY - JOUR T1 - Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis JF - bioRxiv DO - 10.1101/2020.10.12.332569 SP - 2020.10.12.332569 AU - Lynn Radamaker AU - Julian Baur AU - Stefanie Huhn AU - Christian Haupt AU - Ute Hegenbart AU - Stefan Schönland AU - Akanksha Bansal AU - Matthias Schmidt AU - Marcus Fändrich Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/12/2020.10.12.332569.abstract N2 - 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.Competing Interest StatementThe authors have declared no competing interest. ER -