Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis
Articolo
Data di Pubblicazione:
2024
Citazione:
Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis / T. Schulte, A. Chaves-Sanjuan, V. Speranzini, K. Sicking, M. Milazzo, G. Mazzini, P. Rognoni, S. Caminito, P. Milani, C. Marabelli, A. Corbelli, L. Diomede, F. Fiordaliso, L. Anastasia, C. Pappone, G. Merlini, M. Bolognesi, M. Nuvolone, R. Fernández-Busnadiego, G. Palladini, S. Ricagno. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 15:1(2024), pp. 6359.1-6359.11. [10.1038/s41467-024-50686-2]
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
T. Schulte, A. Chaves-Sanjuan, V. Speranzini, K. Sicking, M. Milazzo, G. Mazzini, P. Rognoni, S. Caminito, P. Milani, C. Marabelli, A. Corbelli, L. Diomede, F. Fiordaliso, L. Anastasia, C. Pappone, G. Merlini, M. Bolognesi, M. Nuvolone, R. Fernández-Busnadiego, G. Palladini, S. Ricagno
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