8A7O

beta-2-microglobulin DeltaN6 amyloid fibril form 2PFa

Summary for 8A7O

• Entry DOI: 10.2210/pdb8a7o/pdb
• EMDB information: 15222
• Descriptor: Beta-2-microglobulin form pI 5.3 (1 entity in total)
• Functional Keywords: amyloid, fibril, helical, cross-beta, dialysis-related amyloidosis, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 66920.87

Authors

Wilkinson, M.,Gallardo, R.,Radford, S.E.,Ranson, N.A. (deposition date: 2022-06-21, release date: 2023-03-22, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3 Å)