title: Structure and dynamics of oligomeric intermediates in β2-microglobulin self-assembly.
abstract: 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.
authors: Astbury Centre for Structural Molecular Biology, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
authors: David P
authors: DP
authors: Smith
authors: Lucy A
authors: LA
authors: Woods
authors: Sheena E
authors: SE
authors: Radford
authors: Alison E
authors: AE
authors: Ashcroft
mesh_terms: D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D021241:Spectrometry, Mass, Electrospray Ionization; D001613:beta 2-Microglobulin / Q000737:chemistry*
chemical_list: D001613:beta 2-Microglobulin