Structures of Atg7-Atg3 and Atg7-Atg10 reveal noncanonical mechanisms of E2 recruitment by the autophagy E1 - PubMed (original) (raw)

Structures of Atg7-Atg3 and Atg7-Atg10 reveal noncanonical mechanisms of E2 recruitment by the autophagy E1

Stephen E Kaiser et al. Autophagy. 2013 May.

Abstract

Central to most forms of autophagy are two ubiquitin-like proteins (UBLs), Atg8 and Atg12, which play important roles in autophagosome biogenesis, substrate recruitment to autophagosomes, and other aspects of autophagy. Typically, UBLs are activated by an E1 enzyme that (1) catalyzes adenylation of the UBL C terminus, (2) transiently covalently captures the UBL through a reactive thioester bond between the E1 active site cysteine and the UBL C terminus, and (3) promotes transfer of the UBL C terminus to the catalytic cysteine of an E2 conjugating enzyme. The E2, and often an E3 ligase enzyme, catalyzes attachment of the UBL C terminus to a primary amine group on a substrate. Here, we summarize our recent work reporting the structural and mechanistic basis for E1-E2 protein interactions in autophagy.

Keywords: Atg10; Atg12; Atg3; Atg7; Atg8; E1 enzyme; E2 enzyme; ubiquitin-like protein.

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Figures

Figure 1. Structural analysis of proteins involved in the autophagy ubiquitin-like protein conjugation systems. (A) Domain diagrams for Atg7, Atg3 and Atg10. NTD, N-terminal domain; CTD, C-terminal domain; AD, adenylation domain; ECTD, extreme C-terminal domain; FR, flexible region; HR, handle region; β, β-hairpin. Catalytic cysteine residues are indicated with yellow lines. (B and C) Schematic and structure of the Atg7-Atg3 complex indicating key structural features involved in binding. Catalytic-cysteine thiols are shown as yellow spheres. (D and E) Schematic and structure of the Atg7-Atg10 complex indicating key structural features involved in binding. Yellow spheres represent the catalytic-cysteine thiols of Atg7 and His131 or Pro132 of Atg10, in which the catalytic cysteine was not visible.

Comment on

Kaiser SE, Mao K, Taherbhoy AM, Yu S, Olszewski JL, Duda DM, et al. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures. Nat Struct Mol Biol. 2012;19:1242–9. doi: 10.1038/nsmb.2415.

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Structures of Atg7-Atg3 and Atg7-Atg10 reveal noncanonical mechanisms of E2 recruitment by the autophagy E1 - PubMed (original) (raw)