title: Noncanonical recognition and UBL loading of distinct E2s by autophagy-essential Atg7.
abstract: Autophagy requires ubiquitin-like Atg8 and Atg12 conjugation systems, where Atg7 has a critical role as the sole E1 enzyme. Although Atg7 recognizes two distinct E2s, Atg3 and Atg10, it is not understood how Atg7 correctly loads these E2s with their cognate ubiquitin-like proteins, Atg8 and Atg12. Here, we report the crystal structures of the N-terminal domain of Atg7 bound to Atg10 or Atg3 of thermotolerant yeast and plant homologs. The observed Atg7-Atg10 and Atg7-Atg3 interactions, which resemble each other but are quite distinct from the canonical E1-E2 interaction, makes Atg7 suitable for transferring Atg12 to Atg10 and Atg8 to Atg3 by a trans mechanism. Notably, in vitro experiments showed that Atg7 loads Atg3 and Atg10 with Atg8 and Atg12 in a nonspecific manner, which suggests that cognate conjugate formation in vivo is not an intrinsic quality of Atg7.
authors.affiliation: Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matoba
authors.forename: Ryoko
authors.initials: R
authors.lastname: Sawada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakatogawa
authors.forename: Hayashi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kobashigawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hoshida
authors.forename: Rinji
authors.initials: R
authors.lastname: Akada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohsumi
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Noda
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
mesh_terms: D017360:Arabidopsis / Q000201:enzymology; D001343:Autophagy; D018360:Crystallography, X-Ray; D004951:Esterification; D008958:Models, Molecular; D044764:Ubiquitin-Activating Enzymes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D044764:Ubiquitin-Activating Enzymes