| 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]
Publication Abstract from PubMed
Autophagy is the degradation of cellular organelles via the lysosomal pathway. The autophagic ubiquitin-like (Ubl) molecule Atg8 is activated by the E1-like enzyme Atg7. As this noncanonical E1 enzyme's domain organization is unique among Ubl-activating E1 enzymes, the structural basis for its interactions with Atg8 and partner E2 enzymes remains obscure. Here we present the structure of the N-terminal domain of Atg7, revealing a unique protein fold and interactions with both autophagic E2 enzymes Atg3 and Atg10. The structure of the C-terminal domain of Atg7 in complex with Atg8 shows the mode of dimerization and mechanism of recognition of Atg8. Notably, the catalytic cysteine residue in Atg7 is positioned close to the C-terminal glycine of Atg8, its target for thioester formation, potentially eliminating the need for large conformational rearrangements characteristic of other E1s.
Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8.,Hong SB, Kim BW, Lee KE, Kim SW, Jeon H, Kim J, Song HK Nat Struct Mol Biol. 2011 Nov 6. doi: 10.1038/nsmb.2165. PMID:22056771[10]
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
- ↑ Hong SB, Kim BW, Lee KE, Kim SW, Jeon H, Kim J, Song HK. Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8. Nat Struct Mol Biol. 2011 Nov 6. doi: 10.1038/nsmb.2165. PMID:22056771 doi:10.1038/nsmb.2165
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