3t7e
From Proteopedia
Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway
Structural highlights
Function[ATG7_YEAST] E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 and ATG8 for its conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes.[1] [2] [3] [4] [5] [6] [7] [8] [9] Publication Abstract from PubMedAtg7 is a noncanonical, homodimeric E1 enzyme that interacts with the noncanonical E2 enzyme, Atg3, to mediate conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy. Here we report that the unique N-terminal domain of Atg7 (Atg7(NTD)) recruits a unique "flexible region" from Atg3 (Atg3(FR)). The structure of an Atg7(NTD)-Atg3(FR) complex reveals hydrophobic residues from Atg3 engaging a conserved groove in Atg7, important for Atg8 conjugation. We also report the structure of the homodimeric Atg7 C-terminal domain, which is homologous to canonical E1s and bacterial antecedents. The structures, SAXS, and crosslinking data allow modeling of a full-length, dimeric (Atg7 approximately Atg8-Atg3)(2) complex. The model and biochemical data provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic cysteine of one Atg7 protomer to Atg3 bound to the N-terminal domain of the opposite Atg7 protomer within the homodimer. The studies reveal a distinctive E1 approximately UBL-E2 architecture for enzymes mediating autophagy. Atg8 transfer from atg7 to atg3: a distinctive e1-e2 architecture and mechanism in the autophagy pathway.,Taherbhoy AM, Tait SW, Kaiser SE, Williams AH, Deng A, Nourse A, Hammel M, Kurinov I, Rock CO, Green DR, Schulman BA Mol Cell. 2011 Nov 4;44(3):451-61. PMID:22055190[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Saccharomyces cerevisiae | Deng, A | Green, D R | Hammel, M | Kaiser, S E | Kurinov, I | Nourse, A | Rock, C O | Schulman, B A | Taherbhoy, A M | Tait, S W | Williams, A H | Atg7 | Autophagy | E1 | Ligase
