Structural insights into Atg10-mediated formation of the autophagy-essential Atg12-Atg5 conjugate - PubMed (original) (raw)
. 2012 Jul 3;20(7):1244-54.
doi: 10.1016/j.str.2012.04.018. Epub 2012 Jun 7.
Affiliations
- PMID: 22682742
- DOI: 10.1016/j.str.2012.04.018
Free article
Structural insights into Atg10-mediated formation of the autophagy-essential Atg12-Atg5 conjugate
Masaya Yamaguchi et al. Structure. 2012.
Free article
Abstract
The Atg12-Atg5 conjugate, which is formed by an ubiquitin-like conjugation system, is essential to autophagosome formation, a central event in autophagy. Despite its importance, the molecular mechanism of the Atg12-Atg5 conjugate formation has not been elucidated. Here, we report the solution and crystal structures of Atg10 and Atg5 homologs from Kluyveromyces marxianus (Km), a thermotolerant yeast. KmAtg10 comprises an E2-core fold with characteristic accessories, including two β strands, whereas KmAtg5 has two ubiquitin-like domains and a helical domain. The nuclear magnetic resonance experiments, mutational analyses, and crosslinking experiments showed that KmAtg10 directly recognizes KmAtg5, especially its C-terminal ubiquitin-like domain, by its characteristic two β strands. Kinetic analysis suggests that Tyr56 and Asn114 of KmAtg10 may place the side chain of KmAtg5 Lys145 into the optimal orientation for its conjugation reaction with Atg12. These structural features enable Atg10 to mediate the formation of the Atg12-Atg5 conjugate without a specific E3 enzyme.
Copyright © 2012 Elsevier Ltd. All rights reserved.
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