Disease-relevant β2-microglobulin variants share a common amyloid fold

Martin Wilkinson, Rodrigo U. Gallardo, Roberto Maya Martinez, Nicolas Guthertz, Masatomo So, Liam D. Aubrey, Sheena E. Radford () and Neil A. Ranson ()
Additional contact information
Martin Wilkinson: Faculty of Biological Sciences, University of Leeds
Rodrigo U. Gallardo: Faculty of Biological Sciences, University of Leeds
Roberto Maya Martinez: Faculty of Biological Sciences, University of Leeds
Nicolas Guthertz: Faculty of Biological Sciences, University of Leeds
Masatomo So: Faculty of Biological Sciences, University of Leeds
Liam D. Aubrey: Faculty of Biological Sciences, University of Leeds
Sheena E. Radford: Faculty of Biological Sciences, University of Leeds
Neil A. Ranson: Faculty of Biological Sciences, University of Leeds

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract β2-microglobulin (β2m) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of β2m result in diseases with distinct pathologies. β2m-D76N causes a rare systemic amyloidosis with protein deposited in the viscera in the absence of renal failure, whilst β2m-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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36791-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36791-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36791-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().