Fig. 7
From: Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter
Schematic model of N-degron recognition and pH-dependent regulation of p62. a The ZZ-domain of mammalian p62 recognizes cargo-bound R-BiP or unknown N-degron (type-1 or type-2) proteins (colored lavender). The PB1, ZZ and remaining (LIR and UBA) domains in p62 are colored orange, light green and yellow, respectively. The ZZ-domain of plant PRT1 E3 Ub ligase recognizes bulky aromatic hydrophobic N-degron. The UBR box from yeast Ubr1 and bacterial ClpS protein recognize basic type-1 and hydrophobic type-2 substrates, respectively. b pH-dependent regulation of p62 oligomerization. The R-BiP chaperon (colored lavender) binds to the ubiquitylated aggregate under certain conditions such as stress. The R-BiP containing N-degron is recognized by small-oligomer p62 at physiological pH with very weak affinity (left). p62 forms a long filamentous polymer at lower pH conditions, which might be similar to the environment for forming pre-autophagosomal structures or autophagosomes, and the functional affinity increases markedly via enhanced avidity (middle). The filamentous p62 polymer is converted into smaller-sized oligomers at below pH 5.0, as reflects lysosomal pH conditions, which facilitates release of the substrates from the p62-bound complex (right)
