Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
27 Jul 2024
27 Jul 2024
Historique:
received:
07
05
2024
accepted:
15
07
2024
medline:
28
7
2024
pubmed:
28
7
2024
entrez:
27
7
2024
Statut:
epublish
Résumé
ATTR amyloidosis results from the conversion of transthyretin into amyloid fibrils that deposit in tissues causing organ failure and death. This conversion is facilitated by mutations in ATTRv amyloidosis, or aging in ATTRwt amyloidosis. ATTRv amyloidosis exhibits extreme phenotypic variability, whereas ATTRwt amyloidosis presentation is consistent and predictable. Previously, we found unique structural variabilities in cardiac amyloid fibrils from polyneuropathic ATTRv-I84S patients. In contrast, cardiac fibrils from five genotypically different patients with cardiomyopathy or mixed phenotypes are structurally homogeneous. To understand fibril structure's impact on phenotype, it is necessary to study the fibrils from multiple patients sharing genotype and phenotype. Here we show the cryo-electron microscopy structures of fibrils extracted from four cardiomyopathic ATTRwt amyloidosis patients. Our study confirms that they share identical conformations with minimal structural variability, consistent with their homogenous clinical presentation. Our study contributes to the understanding of ATTR amyloidosis biopathology and calls for further studies.
Identifiants
pubmed: 39068302
doi: 10.1038/s42003-024-06588-6
pii: 10.1038/s42003-024-06588-6
doi:
Substances chimiques
Amyloid
0
Prealbumin
0
TTR protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
905Subventions
Organisme : American Heart Association (American Heart Association, Inc.)
ID : 847236
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : DP2-DL163810
Organisme : Welch Foundation
ID : I-2121-20220331
Informations de copyright
© 2024. The Author(s).
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