Phosphorylation at both Ser-13 and Ser-16 inhibits the aggregation of Httex1-Q42 Q18A, whereas the S13D/S16D Httex1-Q42 Q18A exhibits a marked reduction in aggregation but retains the ability to form fibrils.
A, comparative analysis of the aggregation of diphosphorylated Q18A (pSer-13/pSer-16) and diphosphomimetic (S13D/S16D) mutant (42Q) Httex1 at 2.5 μm using the UHPLC sedimentation assay (error bars, S.D. derived from n = 3 independent experiments). B, CD analysis of the samples at 0 and after 48 h of incubation at room temperature. C, TEM images of the final aggregation time point (48 h). Scale bars, 200 nm.