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

Taherbhoy, A.M. et al. (2011) Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway. Molecular Cell, 44(3), pp. 451-461. (doi:10.1016/j.molcel.2011.08.034)

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Publisher's URL: http://dx.doi.org/10.1016/j.molcel.2011.08.034

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 (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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tait, Professor Stephen
Authors: Taherbhoy, A.M., Tait, S.W.G., Kaiser, S.E., Williams, A.H., Deng, A., Nourse, A., Hammel, M., Kurinov, I., Rock, C.O., Green, D.R., and Schulman, B.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Molecular Cell
Journal Abbr.:Mol Cell
ISSN:1097-2765
ISSN (Online):1097-4164

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