8GBR

Cardiac amyloid fibrils extracted from a wild-type ATTR amyloidosis patient

8GBR の概要

• エントリーDOI: 10.2210/pdb8gbr/pdb
• EMDBエントリー: 26587 26691 29874 29920
• 分子名称: Transthyretin (1 entity in total)
• 機能のキーワード: transthyretin, amyloidosis, systemic amyloidosis, attr, cardiac, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 79524.92

構造登録者

Nguyen, B.A.,Saelices, L. (登録日: 2023-02-28, 公開日: 2024-02-28, 最終更新日: 2024-09-18)

主引用文献

Nguyen, B.A.,Singh, V.,Afrin, S.,Singh, P.,Pekala, M.,Ahmed, Y.,Pedretti, R.,Canepa, J.,Lemoff, A.,Kluve-Beckerman, B.,Wydorski, P.M.,Chhapra, F.,Saelices, L.
Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis.
Commun Biol, 7:905-905, 2024

PubMed Abstract: 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.

PubMed: 39068302
DOI: 10.1038/s42003-024-06588-6

実験手法

ELECTRON MICROSCOPY (3.4 Å)