9BYN

Cryo-EM structure of amyloid fibril extracted from nerve of a variant ATTR V30M amyloidosis patient

Summary for 9BYN

• Entry DOI: 10.2210/pdb9byn/pdb
• EMDB information: 45039
• Descriptor: Transthyretin (1 entity in total)
• Functional Keywords: amyloidosis, systemic amyloidosis, attr, nerve, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 5
• Total formula weight: 69047.13

Authors

Nguyen, A.B.,Afrin, S.,Yakubovska, A.,Saelices, L. (deposition date: 2024-05-23, release date: 2025-03-12)

Primary citation

Nguyen, B.A.,Afrin, S.,Yakubovska, A.,Singh, V.,Pedretti, R.,Bassett, P.,Pekala, M.,Alicea, J.V.,Kunach, P.,Wang, L.,Lemoff, A.,Kluve-Beckerman, B.,Saelices, L.
ATTRv-V30M amyloid fibrils from heart and nerves exhibit structural homogeneity.
Structure, 32:2244-2250.e3, 2024

PubMed Abstract: Amyloidogenic transthyretin (ATTR) amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin. Transthyretin is primarily produced in tetrameric form by the liver, but also by retinal epithelium and choroid plexus. The deposition of these fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryoelectron microscopy (cryo-EM), we investigated fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found consistent fibril structures from both tissues, similar to cardiac fibrils previously described, but different from vitreous humor fibrils of the same genotype. Our findings, along with previous ATTR fibrils structural studies, suggest a uniform fibrillar architecture across different tissues when transthyretin originates from the liver. This study advances our understanding of how deposition and production sites influence fibril structure in ATTRv-V30M amyloidosis.

PubMed: 39423808
DOI: 10.1016/j.str.2024.09.021

Experimental method

ELECTRON MICROSCOPY (3.36 Å)