Figure 7: Accessibility of the htt exon1 fibril PRDs probed by solvent-filtered ssNMR and antibody binding.

(a,b) Solvent accessibility of htt exon1 fibrils prepared at (a) 37 °C and (b) 22 °C probed by ssNMR. Peak intensities after 7 ms ¹H–¹H diffusion from the solvent into the fibrils (blue) are compared to the ¹³C CP spectrum in absence of T₂-based solvent filtering (grey). Each spectrum was normalized to the highest peaks to highlight the relative solvent exposures. Up/down arrows indicate sites with high/low solvent accessibility. The NMR measurements were performed at 275 K on a 600 MHz (¹H) spectrometer. (c) Dot blot analysis shows that in the monomeric protein the polyQ domain, oligoPro segments and PRD tail are all accessible for binding by MW1, MW7 and MW8, respectively (Fig. 1). Upon aggregation at 22 or 37 °C, MW1 binding to the polyQ is largely abolished, while the PRD tail is still strongly recognized by MW8. OligoPro binding by MW7 is weaker in the 22 °C fibrils compared to the 37 °C polymorph.