8TDO

Cryo-EM structure of cardiac amyloid fibril from a variant ATTR I84S amyloidosis patient-3, variant-type morphology

Summary for 8TDO

• Entry DOI: 10.2210/pdb8tdo/pdb
• EMDB information: 26685 27323 41171 41172
• Descriptor: Transthyretin (1 entity in total)
• Functional Keywords: attr, amyloidosis, cardiac fibril, i84s, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 63515.61

Authors

Nguyen, B.A.,Singh, V.,Saelices, L. (deposition date: 2023-07-04, release date: 2023-12-13, Last modification date: 2024-03-13)

Primary citation

Nguyen, B.A.,Singh, V.,Afrin, S.,Yakubovska, A.,Wang, L.,Ahmed, Y.,Pedretti, R.,Fernandez-Ramirez, M.D.C.,Singh, P.,Pekala, M.,Cabrera Hernandez, L.O.,Kumar, S.,Lemoff, A.,Gonzalez-Prieto, R.,Sawaya, M.R.,Eisenberg, D.S.,Benson, M.D.,Saelices, L.
Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy.
Nat Commun, 15:581-581, 2024

PubMed Abstract: ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies.

PubMed: 38233397
DOI: 10.1038/s41467-024-44820-3

Experimental method

ELECTRON MICROSCOPY (3.1 Å)