Structure and dynamics of oligomeric intermediates in β2-microglobulin self-assembly.

SMITH, David, WOODS, L A, RADFORD, S E and ASHCROFT, A E (2011). Structure and dynamics of oligomeric intermediates in β2-microglobulin self-assembly. Biophysical Journal, 101 (5), 1238-1247.

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β(2)-Microglobulin is a 99-residue protein with a propensity to form amyloid-like fibrils in vitro which exhibit distinct morphologies dependent on the solution conditions employed. Here we have used ion mobility spectrometry-mass spectrometry to characterize the oligomeric species detected during the formation of worm-like fibrils of β(2)-microglobulin at pH 3.6. Immediately upon sample dissolution, β(2)-microglobulin monomer and oligomers-the latter ranging in size from dimer to hexamer-are present as a pool of rapidly interconverting species. Increasing the ionic strength of the solution initiates fibril formation without a lag-phase whereupon these oligomers become more stable and higher-order species (7-mer to >14-mer) are observed. The oligomers detected have collision cross-sectional areas consistent with a linearly stacked assembly comprising subunits of native-like volume. The results provide insights into the identity and properties of the transient, oligomeric intermediates formed during assembly of worm-like fibrils and identify species that differ significantly from the oligomers previously characterized during the nucleated assembly of long, straight fibrils. The data presented demonstrate the interrelationship between different fibril-forming pathways and identify their points of divergence.

Item Type: Article
Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomedical Research Centre
Identification Number:
Page Range: 1238-1247
Depositing User: Rebecca Jones
Date Deposited: 08 Mar 2012 09:09
Last Modified: 18 Mar 2021 10:15

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