8A7P

beta-2-microglobulin DeltaN6 amyloid fibril form 2PFb

8A7P の概要

• エントリーDOI: 10.2210/pdb8a7p/pdb
• 関連するPDBエントリー: 8A7O
• EMDBエントリー: 15222 15223 15224 15226 15227
• 分子名称: Beta-2-microglobulin form pI 5.3 (1 entity in total)
• 機能のキーワード: amyloid, fibril, helical, cross-beta, dialysis-related amyloidosis, b2m, polymorph, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 66920.87

構造登録者

Wilkinson, M.,Gallardo, R.,Radford, S.E.,Ranson, N.A. (登録日: 2022-06-21, 公開日: 2023-03-22, 最終更新日: 2024-10-23)

主引用文献

Wilkinson, M.,Gallardo, R.U.,Martinez, R.M.,Guthertz, N.,So, M.,Aubrey, L.D.,Radford, S.E.,Ranson, N.A.
Disease-relevant beta 2 -microglobulin variants share a common amyloid fold.
Nat Commun, 14:1190-1190, 2023

PubMed Abstract: β-microglobulin (βm) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of βm result in diseases with distinct pathologies. βm-D76N causes a rare systemic amyloidosis with protein deposited in the viscera in the absence of renal failure, whilst βm-V27M is associated with renal failure, with amyloid deposits forming predominantly in the tongue. Here we use cryoEM to determine the structures of fibrils formed from these variants under identical conditions in vitro. We show that each fibril sample is polymorphic, with diversity arising from a 'lego-like' assembly of a common amyloid building block. These results suggest a 'many sequences, one amyloid fold' paradigm in contrast with the recently reported 'one sequence, many amyloid folds' behaviour of intrinsically disordered proteins such as tau and Aβ.

PubMed: 36864041
DOI: 10.1038/s41467-023-36791-8

実験手法

ELECTRON MICROSCOPY (3.4 Å)