3T7H

Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway

Summary for 3T7H

• Entry DOI: 10.2210/pdb3t7h/pdb
• Related: 3T7E 3T7F 3T7G
• Descriptor: Ubiquitin-like modifier-activating enzyme ATG7 (2 entities in total)
• Functional Keywords: atg7, autophagy, e1, ligase
• Biological source: Saccharomyces cerevisiae (yeast)
• Cellular location: Cytoplasm: P38862
• Total number of polymer chains: 2
• Total formula weight: 66880.52

Authors

Taherbhoy, A.M.,Tait, S.W.,Kaiser, S.E.,Williams, A.H.,Deng, A.,Nourse, A.,Hammel, M.,Kurinov, I.,Rock, C.O.,Green, D.R.,Schulman, B.A. (deposition date: 2011-07-30, release date: 2011-11-23, Last modification date: 2023-09-13)

Primary citation

Taherbhoy, A.M.,Tait, S.W.,Kaiser, S.E.,Williams, A.H.,Deng, A.,Nourse, A.,Hammel, M.,Kurinov, I.,Rock, C.O.,Green, D.R.,Schulman, B.A.
Atg8 transfer from atg7 to atg3: a distinctive e1-e2 architecture and mechanism in the autophagy pathway.
Mol.Cell, 44:451-461, 2011

PubMed Abstract: Atg7 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~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~UBL-E2 architecture for enzymes mediating autophagy.

PubMed: 22055190
DOI: 10.1016/j.molcel.2011.08.034
PDB entries with the same primary citation

Experimental method

X-RAY DIFFRACTION (1.6 Å)