| Autor: |
Tim Schulte, Antonio Chaves-Sanjuan, Valentina Speranzini, Kevin Sicking, Melissa Milazzo, Giulia Mazzini, Paola Rognoni, Serena Caminito, Paolo Milani, Chiara Marabelli, Alessandro Corbelli, Luisa Diomede, Fabio Fiordaliso, Luigi Anastasia, Carlo Pappone, Giampaolo Merlini, Martino Bolognesi, Mario Nuvolone, Rubén Fernández-Busnadiego, Giovanni Palladini, Stefano Ricagno |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-50686-2 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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