Extended Data Figure 1. Mechanisms of Parkin autoinhibition.

a, Structure of autoinhibited, full-length human Parkin (pdb-id 5c1z, ¹⁹) shown schematically (top, as in Fig. 1a) and in cartoon representation in the same colours. Two insets show the UPD-RING2 interface (with Cys431 shows in ball-and-stick representation), and the blocked E2 binding site (with the E2 position, modelled according to 5edv ²⁹ shown as grey surface). Zn ions are shown as grey spheres. b, An ‘open-book’ view on the UPD-RING2 interface, with hydrophobic residues coloured white on each surface. c, Structure of phospho-ubiquitin bound to full-length Parkin (pdb-id 5n2w, ⁶) as in a. Phospho-ubiquitin binding leads to helix straightening, and IBR domain repositioning, which releases the Ubl domain for phosphorylation^5,6. In the shown structures of unphosphorylated Parkin, the Ubl and REP (red) inhibit E2 binding, and the RING2-UPD interface is intact, with Cys431 being inaccessible. The Ubl-UPD linker was removed from both crystallised constructs^6,22.