3vqi
From Proteopedia
Crystal structure of Kluyveromyces marxianus Atg5
Structural highlights
FunctionATG5_KLUMD Involved in cytoplasm to vacuole transport (Cvt) and autophagic vesicle formation (PubMed:26442587). Autophagy is essential for maintenance of amino acid levels and protein synthesis under nitrogen starvation (By similarity). Required for selective autophagic degradation of the nucleus (nucleophagy) (By similarity). Also required for mitophagy, which eliminates defective or superfluous mitochondria in order to fulfill cellular energy requirements and prevent excess ROS production (By similarity). Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function (PubMed:22682742). The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 and ATG8 association to the vesicle membranes (By similarity). ATG12-ATG5 rearranges the ATG3 catalytic center and enhances its E2 activity (By similarity).[UniProtKB:Q12380][1] [2] Publication Abstract from PubMedThe 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 beta 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 beta 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. Structural insights into atg10-mediated formation of the autophagy-essential atg12-atg5 conjugate.,Yamaguchi M, Noda NN, Yamamoto H, Shima T, Kumeta H, Kobashigawa Y, Akada R, Ohsumi Y, Inagaki F Structure. 2012 Jul 3;20(7):1244-54. Epub 2012 Jun 7. PMID:22682742[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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