Disease-relevant ß2-microglobulin variants share a common amyloid fold.
Nat Commun
; 14(1): 1190, 2023 03 02.
Article
in En
| MEDLINE
| ID: mdl-36864041
ABSTRACT
ß2-microglobulin (ß2m) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of ß2m result in diseases with distinct pathologies. ß2m-D76N causes a rare systemic amyloidosis with protein deposited in the viscera in the absence of renal failure, whilst ß2m-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 Aß.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Renal Insufficiency
/
Amyloidosis
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2023
Document type:
Article
Affiliation country: