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Atg12-Interacting Motif Is Crucial for E2-E3 Interaction in Plant Atg8 System.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2021 Sep 01; Vol. 44 (9), pp. 1337-1343. Date of Electronic Publication: 2021 Jul 01. - Publication Year :
- 2021
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Abstract
- Autophagy is an intracellular degradation system regulating cellular homeostasis. The two ubiquitin-like modification systems named the Atg8 system and the Atg12 system are essential for autophagy. Atg8 and Atg12 are ubiquitin-like proteins covalently conjugated with a phosphatidylethanolamine (PE) and Atg5, respectively, via enzymatic reactions. The Atg8-PE conjugate binds to autophagic membranes and recruits various proteins through direct interaction, whereas the Atg12-Atg5 conjugate recognizes Atg3, the E2 enzyme for Atg8, and facilitates Atg8-PE conjugation by functioning as the E3 enzyme. Although structural and biochemical analyses have well established the Atg8-family interacting motif (AIM), studies on the interacting sequence for Atg12 are rare (only one example for human ATG12-ATG3), thereby making it challenging to define a binding motif. Here we determined the crystal structure of the plant ATG12b as a complex with the ATG12b-binding region of ATG3 and revealed that ATG12b recognizes the aspartic acid (Asp)-methionine (Met) motif in ATG3 via a hydrophobic pocket and a basic residue, which we confirmed critical for the complex formation by mutational analysis. This recognition mode is similar to that reported between human ATG12 and ATG3, suggesting that the Asp-Met sequence is a conserved Atg12-interacting motif (AIM12). These data suggest that AIM12 mediates E2-E3 interaction during Atg8 lipidation and provide structural basis for developing chemicals that regulate autophagy by targeting Atg12-family proteins.
- Subjects :
- Amino Acid Motifs
Arabidopsis Proteins genetics
Arabidopsis Proteins ultrastructure
Autophagy-Related Protein 12 genetics
Autophagy-Related Protein 12 ultrastructure
Autophagy-Related Protein 5 metabolism
Autophagy-Related Protein 8 Family ultrastructure
Crystallography, X-Ray
Mutagenesis, Site-Directed
Phosphatidylethanolamines metabolism
Plant Proteins ultrastructure
Arabidopsis Proteins metabolism
Autophagy
Autophagy-Related Protein 12 metabolism
Autophagy-Related Protein 8 Family metabolism
Plant Proteins metabolism
Ubiquitin-Conjugating Enzymes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 44
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 34193767
- Full Text :
- https://doi.org/10.1248/bpb.b21-00439