7OB4

Cryo-EM structure of a twisted-dimer transthyretin amyloid fibril from vitreous body of the eye

7OB4 の概要

• エントリーDOI: 10.2210/pdb7ob4/pdb
• EMDBエントリー: 12794
• 分子名称: Transthyretin (1 entity in total)
• 機能のキーワード: amyloid fibril, transthyretin, misfolding, protein fibril, attr amyloidosis, v30m variant, ex vivo, vitreous body
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 193331.96

構造登録者

Iakovleva, I.,Sauer-Eriksson, A.E. (登録日: 2021-04-21, 公開日: 2021-12-15, 最終更新日: 2024-07-10)

主引用文献

Iakovleva, I.,Hall, M.,Oelker, M.,Sandblad, L.,Anan, I.,Sauer-Eriksson, A.E.
Structural basis for transthyretin amyloid formation in vitreous body of the eye.
Nat Commun, 12:7141-7141, 2021

PubMed Abstract: Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. Here, we used cryo-EM to structurally characterize vitreous body ATTR fibrils. These structures were distinct from previously characterized heart fibrils, even though both have the same mutation and type A pathology. Differences were observed at several structural levels: in both the number and arrangement of protofilaments, and the conformation of the protein fibril in each layer of protofilaments. Thus, our results show that ATTR protein structure and its assembly into protofilaments in the type A fibrils can vary between patients carrying the same mutation. By analyzing and matching the interfaces between the amino acids in the ATTR fibril with those in the natively folded TTR, we are able to propose a mechanism for the structural conversion of TTR into a fibrillar form.

PubMed: 34880242
DOI: 10.1038/s41467-021-27481-4

実験手法

ELECTRON MICROSCOPY (3.22 Å)