Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins
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Mammalian ATG8 proteins (mATG8s) are essential for selectiveautophagy because they recruit various proteins with LC3-interacting region (LIR) motifs to autophagic membranes. TheRavZ protein, secreted by Legionella pneumophila, and mammalianATG4B possess functional LIR motifs that participate inlipidated mATG8 deconjugation on autophagic membranes. RavZ comprises three functional LIR motifs at the N- and Cterminalsides of its catalytic domain (CAD). This study demonstratedthat LIR motifs at the N-terminal side of the CAD ofRavZ are involved in autophagic membrane targeting andsubstrate recognition, while LIR motif at the C-terminal sidefacilitate autophagic membrane targeting. Our results alsorevealed that the C-terminal LIR motif in human ATG4B ispivotal in delipidating LC3B-phosphatidylethanolamine (PE), butit plays a minor role in pro-LC3B priming in the cytosol. Therefore,introducing a functional LIR motif to the N-terminal ofATG4B does not affect LC3B-PE delipidation. This studyclearly described the position-dependent roles of LIR motifs inRavZ and ATG4B in cellular contexts.
Abstract
Mammalian ATG8 proteins (mATG8s) are essential for selectiveautophagy because they recruit various proteins with LC3-interacting region (LIR) motifs to autophagic membranes. TheRavZ protein, secreted by Legionella pneumophila, and mammalianATG4B possess functional LIR motifs that participate inlipidated mATG8 deconjugation on autophagic membranes. RavZ comprises three functional LIR motifs at the N- and Cterminalsides of its catalytic domain (CAD). This study demonstratedthat LIR motifs at the N-terminal side of the CAD ofRavZ are involved in autophagic membrane targeting andsubstrate recognition, while LIR motif at the C-terminal sidefacilitate autophagic membrane targeting. Our results alsorevealed that the C-terminal LIR motif in human ATG4B ispivotal in delipidating LC3B-phosphatidylethanolamine (PE), butit plays a minor role in pro-LC3B priming in the cytosol. Therefore,introducing a functional LIR motif to the N-terminal ofATG4B does not affect LC3B-PE delipidation. This studyclearly described the position-dependent roles of LIR motifs inRavZ and ATG4B in cellular contexts.
참고문헌 (16)
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