Fig. 1

Schematic representations of PINK1 and PARKIN domains and disease-related mutations. a PINK1 is composed by 581 amino acids, encompassing the mitochondrial targeting sequence (MTS), transmembrane region (TM), N-terminal regulatory region (NT), N-lobe of the kinase domain, C-lobe of the kinase domain and the C-terminal domain (CTD). Mitochondrial processing peptidase (MPP) and presenilin-associated rhomboid-like (PARL) cleavage sites and PINK1 auto-phosphorylation sites are depicted in the figure (S228, T257, S402). b PARKIN is formed by 465 amino acids with a ubiquitin-like domain (UBL), linker, really-interesting-new-gene (RING)/unique Parkin domain (R0/UPD), RING1 (R1), in-between-RING (IBR), repressor element of Parkin (REP), and a RING2 (R2) domain. E2 co-enzyme and p-Ser65-Ub binding sites, as well as Ser65 phosphorylation and Cys431 catalytic sites, are displayed. Disease-associated mutations collected from the movement disorder society genetic mutation (www.mdsgene.org/) and ClinVAR (www.ncbi.nlm.nih.gov/clinvar/) databases are displayed on top of schematic representation. In red are depicted the mutations considered pathogenic