title: Structural insights into E2-E3 interaction for LC3 lipidation.
abstract: The members of the LC3/Atg8 family of proteins are covalently attached to phagophore and autophagosomal membranes. At the last step of the LC3 lipidation cascade, LC3 is transferred from the E2 enzyme ATG3 to phosphatidylethanolamine (PE). This transfer is stimulated by the ATG12-ATG5-ATG16L1 E3 complex, but the mechanism is not fully understood. We recently found that ATG12 of the E3 binds to a short sequence in the flexible region (FR) of ATG3 with high affinity, and that this interaction is critical for E2-E3 complex formation. These findings, together with detailed structural analyses of this interaction, define the properties of ATG12 and provide new insights of how LC3 transfer begins with ATG3 recruitment by ATG12.
authors.affiliation: Department of Integrative Structural and Computational Biology; The Scripps Research Institute; La Jolla, CA USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Metlagel
authors.affiliation: Department of Integrative Structural and Computational Biology; The Scripps Research Institute; La Jolla, CA USA.
authors.forename: Chinatsu
authors.initials: C
authors.lastname: Otomo
authors.affiliation: Department of Integrative Structural and Computational Biology; The Scripps Research Institute; La Jolla, CA USA.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Molecular Bacteriology and Immunology; Graduate School of Medicine; University of the Ryukyus; Okinawa, Japan.
authors.forename: Giichi
authors.initials: G
authors.lastname: Takaesu
authors.affiliation: Department of Integrative Structural and Computational Biology; The Scripps Research Institute; La Jolla, CA USA.
authors.forename: Takanori
authors.initials: T
authors.lastname: Otomo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008840:Microfilament Proteins; D044763:Ubiquitin-Conjugating Enzymes
keywords: Atg8; lipid conjugation; protein structure; protein–peptide interaction; ubiquitin-like protein