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Atg8 Transfer from Atg7 to Atg3: A Distinctive E1-E2 Architecture and Mechanism in the Autophagy Pathway
- Source :
-
Molecular Cell . Nov2011, Vol. 44 Issue 3, p451-461. 11p. - Publication Year :
- 2011
-
Abstract
- Summary: 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 (Atg7NTD) recruits a unique “flexible region” from Atg3 (Atg3FR). The structure of an Atg7NTD-Atg3FR 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENETIC transformation
*AUTOPHAGY
*UBIQUITIN
*ENZYMES
*DIMERIZATION
*BIOCHEMISTRY
Subjects
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 44
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 67210447
- Full Text :
- https://doi.org/10.1016/j.molcel.2011.08.034