Journal
MOLECULAR CELL
Volume 44, Issue 3, Pages 451-461Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2011.08.034
Keywords
-
Categories
Funding
- ALSAC
- St. Jude Cancer Center [NIH5P30CA021765]
- NIH [R01GM077053, R01AI40646, R01GM034496]
- Hartwell Foundation
- Howard Hughes Medical Institute
- NIH NCRR [RR-15301]
- Advanced Photon Source (APS) by US DOE [DE-AC02-05CH11231]
- US DOE Integrated Diffraction Analysis Technologies (IDAT)
- Advanced Light Source (ALS) by US DOE [DE-ACO2-05CH11231]
Ask authors/readers for more resources
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 similar to 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 similar to UBL-E2 architecture for enzymes mediating autophagy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available