3w1s | pdb_00003w1s

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

Structural highlights

3w1s is a 3 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Atg12 is conjugated to Atg5 through enzymatic reactions similar to ubiquitination. The Atg12-Atg5 conjugate functions as an E3-like enzyme to promote lipidation of Atg8, whereas lipidated Atg8 has essential roles in both autophagosome formation and selective cargo recognition during autophagy. However, the molecular role of Atg12 modification in these processes has remained elusive. Here, we report the crystal structure of the Atg12-Atg5 conjugate. In addition to the isopeptide linkage, Atg12 forms hydrophobic and hydrophilic interactions with Atg5, thereby fixing its position on Atg5. Structural comparison with unmodified Atg5 and mutational analyses showed that Atg12 modification neither induces a conformational change in Atg5 nor creates a functionally important architecture. Rather, Atg12 functions as a binding module for Atg3, the E2 enzyme for Atg8, thus endowing Atg5 with the ability to interact with Atg3 to facilitate Atg8 lipidation.

Structure of the Atg12-Atg5 conjugate reveals a platform for stimulating Atg8-PE conjugation.,Noda NN, Fujioka Y, Hanada T, Ohsumi Y, Inagaki F EMBO Rep. 2012 Dec 14. doi: 10.1038/embor.2012.208. PMID:23238393^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

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OCA

[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] 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

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3w1s | pdb_00003w1s

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

Structural highlights

Function

Publication Abstract from PubMed

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References

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