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Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures.

Core functions of autophagy are mediated by ubiquitin-like protein (UBL) cascades, in which a homodimeric E1 enzyme, Atg7, directs the UBLs Atg8 and Atg12 to their respective E2 enzymes, Atg3 and Atg10. Crystallographic and mutational analyses of yeast (Atg7-Atg3)(2) and (Atg7-Atg10)(2) complexes reveal noncanonical, multisite E1-E2 recognition in autophagy. Atg7's unique N-terminal domain recruits distinctive elements from the Atg3 and Atg10 'backsides'. This, along with E1 and E2 conformational variability, allows presentation of 'frontside' Atg3 and Atg10 active sites to the catalytic cysteine in the C-terminal domain from the opposite Atg7 protomer in the homodimer. Despite different modes of binding, the data suggest that common principles underlie conjugation in both noncanonical and canonical UBL cascades, whereby flexibly tethered E1 domains recruit E2s through surfaces remote from their active sites to juxtapose the E1 and E2 catalytic cysteines.

Pubmed ID: 23142976


  • Kaiser SE
  • Mao K
  • Taherbhoy AM
  • Yu S
  • Olszewski JL
  • Duda DM
  • Kurinov I
  • Deng A
  • Fenn TD
  • Klionsky DJ
  • Schulman BA


Nature structural & molecular biology

Publication Data

December 5, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: 5P30CA021765
  • Agency: NIGMS NIH HHS, Id: R01 GM053396
  • Agency: NIGMS NIH HHS, Id: R01 GM077053
  • Agency: NIGMS NIH HHS, Id: R01GM053396
  • Agency: NIGMS NIH HHS, Id: R01GM077053
  • Agency: NCRR NIH HHS, Id: RR-15301
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Autophagy
  • Crystallography, X-Ray
  • Electrophoresis, Polyacrylamide Gel
  • Models, Molecular
  • Protein Conformation
  • Ubiquitin-Activating Enzymes