FIGURE 1.

Schematic representation of Pmel17 proteolytic processing. Shown is a scheme for the primary structure of human Pmel17 and its component domains. Full-length Pmel17 is cleaved first by furin or a related proprotein convertase (PC) into Mα and Mβ fragments. Mα is incorporated into amyloid fibrils and is further proteolytically processed during fibril maturation. Mβ is cleaved by a metalloproteinase (MP), and the resulting C-terminal fragment (CTF) is a target for γ-secretase cleavage, likely facilitating the degradation of Mβ-derived fragments in lysosomes and/or proteasomes. S, signal sequence; NTR, N-terminal region; PKD, polycystic kidney disease protein homology domain; RPT, repeat domain; TM, transmembrane domain; Cyto, cytoplasmic domain.