Fig. 7: DYNLRB1 specific NAGK peptide inhibited NAGK-mediated Q74 clearance.

A Design of NAGK peptide based on the modeled NAGK-DYNLRB1 interaction interface. The upper left panel shows peptide mapping (K⁵⁹AGVDPLVPLR⁶⁹) of the NAGK small domain, and the panel at the lower left shows the interaction between DYNLRB1 and peptide. B Time-course changes in numbers of intermolecular contacts during MDS. The right upper panel shows the number of hydrogen bonds formed between NAGK peptide and DYNLRB1 in a 50 ns MDS, while the right lower panel shows a heatmap representing magnitudes of inter-residue contact formation between NAGK peptide and DYNLRB1 over the simulation. C Transfection of NAGK peptide inhibited the NAGK-mediated suppression of Q74 aggregates in the cellular HD model (HEK293T). HEK293T cells were initially co-transfected with pQ74 and pDsRed2 or pDsRed2-NAGK (representative immunofluorescence images are shown in the left and middle panels). The HEK293T cells initially co-transfected with pQ74 and pDsRed2-NAGK were then re-transfected 6 h later with the NAGK-D_S derived peptide (K⁵⁹AGVDPLVPLR⁶⁹, right panel), and further incubated for 48 h (right panel). Green puncta represent Q74 aggregates. The lower panel represents statistics and shows transfection with the peptide significantly increased the proportion of cells containing aggregates. ***p < 0.0001, n = 100, scale bar = 20 µm.