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

Abstract

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.

Authors:
; ; ; ; ; ; ; ; ; ;  [1];  [2];  [2];  [2];  [2]
  1. Cornell
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OTHERNIHHHMI
OSTI Identifier:
1057298
Resource Type:
Journal Article
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 19; Journal Issue: 12; Journal ID: ISSN 1545-9993
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Kaiser, Stephen E, Mao, Kai, Taherbhoy, Asad M, Yu, Shanshan, Olszewski, Jennifer L, Duda, David M, Kurinov, Igor, Deng, Alan, Fenn, Timothy D, Klionsky, Daniel J, Schulman, Brenda A, Stanford), Michigan), Tennessee-HSC), and SJCH). Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures. United States: N. p., 2012. Web. doi:10.1038/nsmb.2415.
Kaiser, Stephen E, Mao, Kai, Taherbhoy, Asad M, Yu, Shanshan, Olszewski, Jennifer L, Duda, David M, Kurinov, Igor, Deng, Alan, Fenn, Timothy D, Klionsky, Daniel J, Schulman, Brenda A, Stanford), Michigan), Tennessee-HSC), & SJCH). Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures. United States. doi:10.1038/nsmb.2415.
Kaiser, Stephen E, Mao, Kai, Taherbhoy, Asad M, Yu, Shanshan, Olszewski, Jennifer L, Duda, David M, Kurinov, Igor, Deng, Alan, Fenn, Timothy D, Klionsky, Daniel J, Schulman, Brenda A, Stanford), Michigan), Tennessee-HSC), and SJCH). Sun . "Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures". United States. doi:10.1038/nsmb.2415.
@article{osti_1057298,
title = {Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures},
author = {Kaiser, Stephen E and Mao, Kai and Taherbhoy, Asad M and Yu, Shanshan and Olszewski, Jennifer L and Duda, David M and Kurinov, Igor and Deng, Alan and Fenn, Timothy D and Klionsky, Daniel J and Schulman, Brenda A and Stanford) and Michigan) and Tennessee-HSC) and SJCH)},
abstractNote = {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.},
doi = {10.1038/nsmb.2415},
journal = {Nature Structural & Molecular Biology},
issn = {1545-9993},
number = 12,
volume = 19,
place = {United States},
year = {2012},
month = {11}
}