Figure 4. Disease mutations accelerate hnRNPA2 and hnRNPA1 fibrillization.
a. Synthetic hexapeptides A2 wild-type (NYNDFG) or mutant (NYNVFG) were incubated at 25°C for 2h. Fibrillization was monitored by ThT fluorescence. b. EM of A2 wild-type or mutant hexapeptides after 10min at 25°C. Bar, 0.1µm. c–d. Fibrillization analysis of A1 wild-type (SYNDFG) or mutant (SYNVFG) as in (a–b). e. Full-length hnRNPA2 WT, hnRNPA2 D290V, or hnRNP2Δ287–292 was incubated at 25 °C with agitation for 0–12h. At various times, the amount of aggregated hnRNPA2 was determined. Values represent means ± SEM (n=3). f. EM of hnRNPA2 fibrillization reactions after 0, 4, and 12h at 25°C. Note the absence of fibers after 4h for hnRNPA2 wild-type. Bar, 0.5µm. g–h. Fibrillization of full-length hnRNPA1 wild-type, hnRNPA1-D262V, hnRNPA1-D262N, or hnRNPA1Δ259–264 monitored as in (e, f).