Structure of ATTRv-F64S fibrils isolated from skin tissue of a living patient.

Yu, Jun; Zhang, Xuefeng; Pinton, Sandra; Vacchi, Elena; Cavalli, Andrea; Pecoraro, Matteo; Melli, Giorgia; Boland, Andreas · Nat Commun · 2025

basic_science · Level V

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Abstract

Amyloid transthyretin-derived (ATTR) amyloidosis is a degenerative, systemic disease characterized by transthyretin fibril deposition in organs like the heart, kidneys, liver, and skin. In this study, we report the cryo-EM structure of transthyretin fibrils isolated from skin tissue of a living patient carrying a rare genetic mutation (ATTRv F64S). The structure adopts a highly conserved fold previously observed in other ATTR fibrils from various tissues or different genetic variants. Mass spectrometry was used to evaluate fibril content and to identify common post-translational modifications. The structural consistency between ATTR filaments from different tissues or patients validates non-invasive skin biopsy as a diagnostic tool.

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