We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis.
- Authors
Radamaker, Lynn; Baur, Julian; Huhn, Stefanie; Haupt, Christian; Hegenbart, Ute; Schönland, Stefan; Bansal, Akanksha; Schmidt, Matthias; Fändrich, Marcus
- Abstract
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 two ex vivo fibril structures of a λ3 LC. The fibrils were extracted from the explanted heart of a patient (FOR005) and consist of 115-residue fibril proteins, 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. Systemic AL amyloidosis is a protein misfolding disease caused by the aggregation and fibrillation of immunoglobulin light chains (LCs). Here, the authors present the cryo-EM structures of λ3 LC-derived amyloid fibrils that were isolated from patient tissue and they observe structural breaks, where the two different fibril structures co-exist at different z-axial positions within the same fibril.
- Subjects
AMYLOIDOSIS; AMYLOID; PROTEIN folding; CARDIAC patients
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-21126-2