BMB Reports : eISSN 1976-670X

Download original image
Fig. 4. Schematic model of the molecular mechanism of autophagosome targeting of RavZ proteins and RavZ mutants. (A) RavZ proteins can target autophagic membranes via two complementary pathways. One major pathway is mediated by the α3 helix in the catalytic domain and the MT domain via weak membrane association and PI3P binding. Another pathway is mediated by the α3 helix in the catalytic domain and the LIR motifs, via weak membrane association and mATG8 binding. The catalytic domain of RavZ hydrolyzes the amide bond between the C-terminal glycine residue and an adjacent aromatic residue of all forms of mATG8 proteins on autophagic membranes. Therefore, RavZ proteins delipidate mATG8-PE irreversibly. However, it is not clear whether the LIR motifs ahead of the catalytic domain may be involved in substrate recognition on autophagic membranes. (B) The mATG8 binding-deficient RavZ mutant (RavZmLIR1/2–3) can target autophagic membranes by the α3 helix in the catalytic domain and the MT domain via weak membrane association and PI3P binding. The catalytic domain of RavZmLIR1/2–3 can delipidate all forms of mATG8-PE on autophagic membranes. (C) RavZ(ΔMT), the MT domain deletion mutant of RavZ, can target autophagic membranes by the α3 helix in the catalytic domain and the LIR motifs, via weak membrane association and mATG8 binding. The catalytic domain of RavZ(ΔMT) can delipidate LC3B-PE or GABARAP-PE, but not LC3C-PE, on autophagic membranes in an LIR motif-dependent manner.
BMB Reports 2019;52:700~705 https://doi.org/10.5483/BMBRep.2019.52.12.211
© BMB Rep.