Figure 2. Analysis of the TorsinA-LULL1 interface.
(A) Side-by-side comparison of TorsinA-ATP-LULL1 (left) and TorsinAΔE-ATP-LULL1 (right). Zoomed insets show the atomic details of the interactions between TorsinA/TorsinAΔE and LULL1, with a focus on the ΔE303 area. (B and C) Mutational analysis of the TorsinA-LULL1 interface. Substitution or deletion of residues involved in TorsinA-LULL1 binding were probed using a Ni-affinity co-purification assay with recombinant, bacterial-expressed protein. Only TorsinA is His-tagged. SDS-PAGE analysis is shown. Lack of binding is observed by the absence of complex (uncomplexed His-tagged TorsinA is insoluble). t, total lysate, e, Ni eluate. Asterisk denotes an unrelated contaminant.
Figure 2—figure supplement 1. Structural mapping of mutations causing dystonia.
All known point mutations and deletions that lead to dystonia are marked as green dots and shown in light green color, respectively, on the TorsinA-ATP-LULL1 structure. A modifier TorsinA mutation, D216H, is marked as a blue dot. The structural equivalent of the LAP1 missense mutation (E482A) is LULL1 E368A, marked as a green dot. See Table 2 for an explanation of the likely structural consequence.