9XMG

Cryo-EM structure of ATTRA97S amyloid fibrils extracted from patient-derived abdominal adipose biopsy tissue (patient 2).

Summary for 9XMG

• Entry DOI: 10.2210/pdb9xmg/pdb
• EMDB information: 67024
• Descriptor: Transthyretin (1 entity in total)
• Functional Keywords: amyloid, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 5
• Total formula weight: 68966.80

Authors

Ma, B.Y.,Yao, Y.X.,Li, D.,Liu, C. (deposition date: 2025-11-10, release date: 2026-07-22)

Primary citation

Ma, B.,Yao, Y.,Wang, Q.,Zhao, Q.,Liu, K.,Chen, F.,Cheng, H.,Zhang, R.,Liu, C.,Li, D.
Structures of dye-bound transthyretin amyloid fibrils from abdominal fat biopsies.
Nat Commun, 17:-, 2026

PubMed Abstract: Transthyretin (TTR) amyloidosis is a protein misfolding disease characterized by amyloid fibril deposition in vital organs, leading to cardiomyopathy (ATTR-CM). Early diagnosis of ATTR-CM remains challenging due to lack of sensitive, rapid screening methods. Here, we report cryo-EM structures of TTR amyloid fibrils extracted from minimally invasive abdominal fat-pad biopsies of three living Ala97Ser ATTR-CM patients. The adipose-derived fibril structures closely mirror those from diseased post-mortem cardiac tissues, validating the use of fat-pad biopsies to investigate the atomic structure of TTR fibrils in living patients. Furthermore, we determined cryo-EM structures of TTR fibrils in complex with two amyloid-binding dyes, Congo Red (CR) and Thioflavin S (ThS), which are widely used in the clinical diagnosis of ATTR-CM. Both CR and ThS predominantly bind to a specific surface arginine site on the TTR fibril via electrostatic interactions. These findings provide structural insights into how small-molecule dyes bind TTR fibrils, offering a molecular foundation for the rational design of TTR-specific tracers to enable early and accurate diagnosis of TTR amyloidosis.

PubMed: 42026093
DOI: 10.1038/s41467-026-72441-5

Experimental method

ELECTRON MICROSCOPY (3.3 Å)