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Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation
Author(s) -
Abreu Susana,
Kriegenburg Franziska,
GómezSánchez Rubén,
Mari Muriel,
SánchezWandelmer Jana,
Skytte Rasmussen Mads,
Soares Guimarães Rodrigo,
Zens Bettina,
Schuschnig Martina,
Hardenberg Ralph,
Peter Matthias,
Johansen Terje,
Kraft Claudine,
Martens Sascha,
Reggiori Fulvio
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643146
Subject(s) - library science , center (category theory) , computer science , chemistry , crystallography
Deconjugation of the Atg8/ LC 3 protein family members from phosphatidylethanolamine ( PE ) by Atg4 proteases is essential for autophagy progression, but how this event is regulated remains to be understood. Here, we show that yeast Atg4 is recruited onto autophagosomal membranes by direct binding to Atg8 via two evolutionarily conserved Atg8 recognition sites, a classical LC 3‐interacting region ( LIR ) at the C‐terminus of the protein and a novel motif at the N‐terminus. Although both sites are important for Atg4–Atg8 interaction in vivo , only the new N‐terminal motif, close to the catalytic center, plays a key role in Atg4 recruitment to autophagosomal membranes and specific Atg8 deconjugation. We thus propose a model where Atg4 activity on autophagosomal membranes depends on the cooperative action of at least two sites within Atg4, in which one functions as a constitutive Atg8 binding module, while the other has a preference toward PE ‐bound Atg8.