6GK3

Two protofilament beta-2-microglobulin amyloid fibril

Summary for 6GK3

• Entry DOI: 10.2210/pdb6gk3/pdb
• EMDB information: 0014
• Descriptor: Beta-2-microglobulin (1 entity in total)
• Functional Keywords: amyloid, b2m, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 8
• Total formula weight: 61083.57

Authors

Iadanza, M.G.,Ranson, N.A. (deposition date: 2018-05-18, release date: 2018-11-14, Last modification date: 2024-10-23)

Primary citation

Iadanza, M.G.,Silvers, R.,Boardman, J.,Smith, H.I.,Karamanos, T.K.,Debelouchina, G.T.,Su, Y.,Griffin, R.G.,Ranson, N.A.,Radford, S.E.
The structure of a beta2-microglobulin fibril suggests a molecular basis for its amyloid polymorphism.
Nat Commun, 9:4517-4517, 2018

PubMed Abstract: All amyloid fibrils contain a cross-β fold. How this structure differs in fibrils formed from proteins associated with different diseases remains unclear. Here, we combine cryo-EM and MAS-NMR to determine the structure of an amyloid fibril formed in vitro from β-microglobulin (βm), the culprit protein of dialysis-related amyloidosis. The fibril is composed of two identical protofilaments assembled from subunits that do not share βm's native tertiary fold, but are formed from similar β-strands. The fibrils share motifs with other amyloid fibrils, but also contain unique features including π-stacking interactions perpendicular to the fibril axis and an intramolecular disulfide that stabilises the subunit fold. We also describe a structural model for a second fibril morphology and show that it is built from the same subunit fold. The results provide insights into the mechanisms of fibril formation and the commonalities and differences within the amyloid fold in different protein sequences.

PubMed: 30375379
DOI: 10.1038/s41467-018-06761-6

Experimental method

ELECTRON MICROSCOPY (3.975 Å)