Structural mapping of oligomeric intermediates in an amyloid assembly pathway - dataset

Transiently populated oligomers are commonly formed in the early stages of amyloid assembly. Determining the structure(s) of these species and defining their role(s) in assembly are key to developing routes to prevent or delay disease. Here, using a combination of chemical kinetics, NMR spectroscopy, native mass spectrometry and other biophysical methods, we identify and structurally characterise the oligomers required for amyloid assembly of the naturally occurring variant of β2-microglobulin, DN6. The results reveal a remarkably specific assembly pathway involving the formation hexamers that are non-toxic and retain a native-like immunoglobulin fold, but in which the C-terminal strand is unfurled ready to initiate the transition into the amyloid fold. The results suggest new avenues to combat disease by specific targeting of the early intermediates in amyloid assembly.