8G9R

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

Summary for 8G9R

• Entry DOI: 10.2210/pdb8g9r/pdb
• Related: 8E7D 8E7H
• EMDB information: 26587 26691 29874
• Descriptor: Transthyretin (1 entity in total)
• Functional Keywords: transthyretin, amyloidosis, systemic amyloidosis, attr, cardiac, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 5
• Total formula weight: 79524.92

Authors

Nguyen, B.A.,Saelices, L. (deposition date: 2023-02-21, release date: 2024-02-21, Last modification date: 2024-09-18)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.28 Å)