Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins

초록

Mammalian ATG8 proteins (mATG8s) are essential for selective autophagy because they recruit various proteins with LC3- interacting region (LIR) motifs to autophagic membranes. The RavZ protein, secreted by Legionella pneumophila, and mam-malian ATG4B possess functional LIR motifs that participate in lipidated mATG8 deconjugation on autophagic membranes. RavZ comprises three functional LIR motifs at the N- and C- terminal sides of its catalytic domain (CAD). This study demo-nstrated that LIR motifs at the N-terminal side of the CAD of RavZ are involved in autophagic membrane targeting and substrate recognition, while LIR motif at the C-terminal side facilitate autophagic membrane targeting. Our results also revealed that the C-terminal LIR motif in human ATG4B is pivotal in delipidating LC3B-phosphatidylethanolamine (PE), but it plays a minor role in pro-LC3B priming in the cytosol. There-fore, introducing a functional LIR motif to the N-terminal of ATG4B does not affect LC3B-PE delipidation. This study clearly described the position-dependent roles of LIR motifs in RavZ and ATG4B in cellular contexts. [BMB Reports 2024; 57(11): 497-502].

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