We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis.
- Authors
Schulte, Tim; Chaves-Sanjuan, Antonio; Speranzini, Valentina; Sicking, Kevin; Milazzo, Melissa; Mazzini, Giulia; Rognoni, Paola; Caminito, Serena; Milani, Paolo; Marabelli, Chiara; Corbelli, Alessandro; Diomede, Luisa; Fiordaliso, Fabio; Anastasia, Luigi; Pappone, Carlo; Merlini, Giampaolo; Bolognesi, Martino; Nuvolone, Mario; Fernández-Busnadiego, Rubén; Palladini, Giovanni
- Abstract
Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. The double-layered structure displays a u-shaped core that is closed by a β-arc lid and extended by a straight tail. Noteworthy, the fibril harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report structural evidence of interactions between amyloid and collagen, potentially signifying a distinct pathophysiological mechanism of amyloid deposits.Here the authors report the cryo-EM structure of heart-derived fibrils of an AL amyloidosis patient. Surprisingly, the fibrils form helical superstructures with collagen VI, potentially signifying a distinct pathophysiological mechanism for amyloidoses.
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-50686-2