| Structural highlights
Function
[ATG7_YEAST] E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 and ATG8 for its conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes.[1] [2] [3] [4] [5] [6] [7] [8] [9] [ATG8_YEAST] Involved in cytoplasm to vacuole transport (Cvt) vesicles and autophagosomes formation. With ATG4, may mediate the delivery of the vesicles and autophagosomes to the vacuole via the microtubule cytoskeleton. Participates also in membrane fusion events that take place in the early secretory pathway.[10] [11] [12] [13] [14] [15] [16] [17] [18]
Publication Abstract from PubMed
Atg8 is a unique ubiquitin-like protein that is covalently conjugated with a phosphatidylethanolamine through reactions similar to ubiquitination and plays essential roles in autophagy. Atg7 is the E1 enzyme for Atg8, and it activates the C-terminal Gly116 of Atg8 using ATP. Here, we report the crystal structure of Atg8 bound to the C-terminal domain of Atg7 in an unprecedented mode. Atg8 neither contacts with the central beta-sheet nor binds to the catalytic site of Atg7, both of which were observed in previously reported Atg7-Atg8 structures. Instead, Atg8 binds to the C-terminal alpha-helix and crossover loop, thereby changing the autoinhibited conformation of the crossover loop observed in the free Atg7 structure into a short helix and a disordered loop. Mutational analyses suggested that this interaction mode is important for the activation reaction. We propose that Atg7 recognizes Atg8 through multiple steps, which would be necessary to induce a conformational change in Atg7 that is optimal for the activation reaction.
Atg7 Activates an Autophagy-Essential Ubiquitin-like Protein Atg8 through Multi-Step Recognition.,Yamaguchi M, Satoo K, Suzuki H, Fujioka Y, Ohsumi Y, Inagaki F, Noda NN J Mol Biol. 2018 Feb 2;430(3):249-257. doi: 10.1016/j.jmb.2017.12.002. Epub 2017 , Dec 10. PMID:29237558[19]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, Klionsky DJ, Ohsumi M, Ohsumi Y. A protein conjugation system essential for autophagy. Nature. 1998 Sep 24;395(6700):395-8. PMID:9759731 doi:10.1038/26506
- ↑ Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993 Oct 25;333(1-2):169-74. PMID:8224160
- ↑ Harding TM, Morano KA, Scott SV, Klionsky DJ. Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 1995 Nov;131(3):591-602. PMID:7593182
- ↑ Kim J, Dalton VM, Eggerton KP, Scott SV, Klionsky DJ. Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways. Mol Biol Cell. 1999 May;10(5):1337-51. PMID:10233148
- ↑ Tanida I, Mizushima N, Kiyooka M, Ohsumi M, Ueno T, Ohsumi Y, Kominami E. Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy. Mol Biol Cell. 1999 May;10(5):1367-79. PMID:10233150
- ↑ Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y. A ubiquitin-like system mediates protein lipidation. Nature. 2000 Nov 23;408(6811):488-92. PMID:11100732 doi:10.1038/35044114
- ↑ Kim J, Huang WP, Klionsky DJ. Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol. 2001 Jan 8;152(1):51-64. PMID:11149920
- ↑ Yamazaki-Sato H, Tanida I, Ueno T, Kominami E. The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation. FEBS Lett. 2003 Sep 11;551(1-3):71-7. PMID:12965207
- ↑ Ichimura Y, Imamura Y, Emoto K, Umeda M, Noda T, Ohsumi Y. In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy. J Biol Chem. 2004 Sep 24;279(39):40584-92. Epub 2004 Jul 23. PMID:15277523 doi:10.1074/jbc.M405860200
- ↑ Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993 Oct 25;333(1-2):169-74. PMID:8224160
- ↑ Harding TM, Morano KA, Scott SV, Klionsky DJ. Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 1995 Nov;131(3):591-602. PMID:7593182
- ↑ Lang T, Schaeffeler E, Bernreuther D, Bredschneider M, Wolf DH, Thumm M. Aut2p and Aut7p, two novel microtubule-associated proteins are essential for delivery of autophagic vesicles to the vacuole. EMBO J. 1998 Jul 1;17(13):3597-607. PMID:9649430 doi:10.1093/emboj/17.13.3597
- ↑ Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T, Noda T, Ohsumi Y. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol. 1999 Oct 18;147(2):435-46. PMID:10525546
- ↑ Huang WP, Scott SV, Kim J, Klionsky DJ. The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J Biol Chem. 2000 Feb 25;275(8):5845-51. PMID:10681575
- ↑ Legesse-Miller A, Sagiv Y, Glozman R, Elazar Z. Aut7p, a soluble autophagic factor, participates in multiple membrane trafficking processes. J Biol Chem. 2000 Oct 20;275(42):32966-73. PMID:10837468 doi:10.1074/jbc.M000917200
- ↑ Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, Ohsumi M, Takao T, Noda T, Ohsumi Y. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J Cell Biol. 2000 Oct 16;151(2):263-76. PMID:11038174
- ↑ Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y. A ubiquitin-like system mediates protein lipidation. Nature. 2000 Nov 23;408(6811):488-92. PMID:11100732 doi:10.1038/35044114
- ↑ Kim J, Huang WP, Klionsky DJ. Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol. 2001 Jan 8;152(1):51-64. PMID:11149920
- ↑ Yamaguchi M, Satoo K, Suzuki H, Fujioka Y, Ohsumi Y, Inagaki F, Noda NN. Atg7 Activates an Autophagy-Essential Ubiquitin-like Protein Atg8 through Multi-Step Recognition. J Mol Biol. 2018 Feb 2;430(3):249-257. doi: 10.1016/j.jmb.2017.12.002. Epub 2017 , Dec 10. PMID:29237558 doi:https://dx.doi.org/10.1016/j.jmb.2017.12.002
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