Autophagy, a cellular process whereby a double-membrane vesicle engulfs a portion of the cytoplasm and fuses with the lysosome, leading to the degradation of the engulfed contents, is mediated in part by noncanonical ubiquitin-like protein cascades. Atg7, an E1 enzyme, activates the E2 enzymes Atg3 and Atg10. Kaiser et al. and Yamaguchi et al. report crystal structures of the E1–E2 complexes, Atg7–Atg3 and Atg7–Atg10, demonstrating that Atg7 binds both E2 enzymes via the same surface but that the specific amino acids driving the interactions are distinct between the complexes. Both groups also demonstrate in biochemical assays that Atg7 can mediate unexpected conjugation of ubiquitin-like proteins (UBLs) Atg8 and Atg12, transferring them to both E2 enzymes rather than specifying Atg8–Atg3 and Atg12–Atg10 conjugations. Kaiser et al. further confirmed that amino acids essential for Atg7-Atg3 interaction were also necessary to rescue autophagy in Δatg7 or Δatg3 yeast cells. Taken together, these data indicate that E1 enzymes can use the same surface to bind distinct elements from disparate E2 enzymes and that specificity for selective loading of UBLs onto Atg3 and Atg10 observed in vivo might be mediated by elements in addition to Atg7.
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Donner, A. E2 loader. Nat Chem Biol 9, 8 (2013). https://doi.org/10.1038/nchembio.1145
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DOI: https://doi.org/10.1038/nchembio.1145
