3w1s

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Template:STRUCTURE 3w1s

Contents

Crystal structure of Saccharomyces cerevisiae Atg12-Atg5 conjugate bound to the N-terminal domain of Atg16

Template:ABSTRACT PUBMED 23238393

Function

[ATG5_YEAST] Involved in cytoplasm to vacuole transport (Cvt) and autophagy vesicles formation. Required for ATG8 association to the vesicle membranes.[1] [2] [3] [4] [5] [6] [ATG12_YEAST] Ubiquitin-like protein involved in cytoplasm to vacuole transport (Cvt), autophagy vesicles formation, mitophagy, and nucleophagy. Conjugation with ATG5 through an ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 and ATG8 association to the vesicle membranes. ATG12-ATG5 rearranges the ATG3 catalytic center and enhances its E2 activity.[7] [8] [9] [ATG16_YEAST] Stabilizes the ATG5-ATG12 conjugate and mediates the formation of the 350 kDa complex, which is necessary for autophagy. Required for ATG8 localization to the pre-autophagosomal structure.[10] [11] [12] [13] [14]

About this Structure

3w1s is a 3 chain structure with sequence from Saccharomyces cerevisiae s288c. Full crystallographic information is available from OCA.

Reference

  • Noda NN, Fujioka Y, Hanada T, Ohsumi Y, Inagaki F. Structure of the Atg12-Atg5 conjugate reveals a platform for stimulating Atg8-PE conjugation. EMBO Rep. 2012 Dec 14. doi: 10.1038/embor.2012.208. PMID:23238393 doi:10.1038/embor.2012.208
  1. ↑ Kametaka S, Matsuura A, Wada Y, Ohsumi Y. Structural and functional analyses of APG5, a gene involved in autophagy in yeast. Gene. 1996 Oct 31;178(1-2):139-43. PMID:8921905
  2. ↑ 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
  3. ↑ 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
  4. ↑ Mizushima N, Noda T, Ohsumi Y. Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. EMBO J. 1999 Jul 15;18(14):3888-96. PMID:10406794 doi:10.1093/emboj/18.14.3888
  5. ↑ George MD, Baba M, Scott SV, Mizushima N, Garrison BS, Ohsumi Y, Klionsky DJ. Apg5p functions in the sequestration step in the cytoplasm-to-vacuole targeting and macroautophagy pathways. Mol Biol Cell. 2000 Mar;11(3):969-82. PMID:10712513
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ 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
  10. ↑ 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
  11. ↑ Harding TM, Hefner-Gravink A, Thumm M, Klionsky DJ. Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway. J Biol Chem. 1996 Jul 26;271(30):17621-4. PMID:8663607
  12. ↑ Mizushima N, Noda T, Ohsumi Y. Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway. EMBO J. 1999 Jul 15;18(14):3888-96. PMID:10406794 doi:10.1093/emboj/18.14.3888
  13. ↑ Suzuki K, Kirisako T, Kamada Y, Mizushima N, Noda T, Ohsumi Y. The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 2001 Nov 1;20(21):5971-81. PMID:11689437 doi:10.1093/emboj/20.21.5971
  14. ↑ Kuma A, Mizushima N, Ishihara N, Ohsumi Y. Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J Biol Chem. 2002 May 24;277(21):18619-25. Epub 2002 Mar 15. PMID:11897782 doi:10.1074/jbc.M111889200

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