Proteopedia

6kyb

Crystal structure of Atg18 from Saccharomyces cerevisiaeCrystal structure of Atg18 from Saccharomyces cerevisiae

Structural highlights

6kyb is a 4 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 2.8Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ATG18_YEAST The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). May negatively regulate FAB1 activity by sequestering or masking VAC7 from FAB1. Necessary for proper vacuole morphology. Plays an important role in osmotically-induced vacuole fragmentation. Required for cytoplasm to vacuole transport (Cvt) vesicle formation, pexophagy and starvation-induced autophagy. Involved in correct ATG9 trafficking to the pre-autophagosomal structure. Might also be involved in premeiotic DNA replication. With ATG2, protects ATG8 from ATG4-mediated cleavage.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]

Publication Abstract from PubMed

Macroautophagy (hereafter referred to as autophagy) is a highly conserved catabolic eukaryotic pathway that is critical for stress responses and homeostasis. Atg18, one of the core proteins involved in autophagy, belongs to the PROPPIN family and is composed of seven WD40 repeats. Together with Atg2, Atg18 participates in the elongation of phagophores and the recycling of Atg9 in yeast. Despite extensive studies on the PROPPIN family, the structure of Atg18 from Saccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 A. Based on bioinformatics and structural analysis, we found that the 7AB loop of ScAtg18 is extended in Atg18, in comparison to other members of the PROPPIN family. Genetic analysis revealed that the 7AB loop of ScAtg18 is required for autophagy. Biochemical and biophysical experiments indicated that the 7AB loop of ScAtg18 is critical for interaction with ScAtg2 and the recruitment of ScAtg2 to the autophagy-initiating site. Collectively, our results show that the 7AB loop of ScAtg18 is a new binding site for Atg2 and is of functional importance to autophagy.

The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae.,Lei Y, Tang D, Liao G, Xu L, Liu S, Chen Q, Li C, Duan J, Wang K, Wang J, Sun B, Li Z, Dai L, Cheng W, Qi S, Lu K Cell Mol Life Sci. 2020 Aug 18. pii: 10.1007/s00018-020-03621-9. doi:, 10.1007/s00018-020-03621-9. PMID:32809042[18]

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

See Also

References

  1. ↑ Rabitsch KP, Toth A, Galova M, Schleiffer A, Schaffner G, Aigner E, Rupp C, Penkner AM, Moreno-Borchart AC, Primig M, Esposito RE, Klein F, Knop M, Nasmyth K. A screen for genes required for meiosis and spore formation based on whole-genome expression. Curr Biol. 2001 Jul 10;11(13):1001-9. PMID:11470404
  2. ↑ Georgakopoulos T, Koutroubas G, Vakonakis I, Tzermia M, Prokova V, Voutsina A, Alexandraki D. Functional analysis of the Saccharomyces cerevisiae YFR021w/YGR223c/YPL100w ORF family suggests relations to mitochondrial/peroxisomal functions and amino acid signalling pathways. Yeast. 2001 Sep 15;18(12):1155-71. PMID:11536337 doi:http://dx.doi.org/10.1002/yea.764
  3. ↑ Barth H, Meiling-Wesse K, Epple UD, Thumm M. Autophagy and the cytoplasm to vacuole targeting pathway both require Aut10p. FEBS Lett. 2001 Nov 9;508(1):23-8. PMID:11707261
  4. ↑ Guan J, Stromhaug PE, George MD, Habibzadegah-Tari P, Bevan A, Dunn WA Jr, Klionsky DJ. Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy, and autophagy in Saccharomyces cerevisiae and Pichia pastoris. Mol Biol Cell. 2001 Dec;12(12):3821-38. PMID:11739783
  5. ↑ Reggiori F, Tucker KA, Stromhaug PE, Klionsky DJ. The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev Cell. 2004 Jan;6(1):79-90. PMID:14723849
  6. ↑ Stromhaug PE, Reggiori F, Guan J, Wang CW, Klionsky DJ. Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy. Mol Biol Cell. 2004 Aug;15(8):3553-66. Epub 2004 May 21. PMID:15155809 doi:http://dx.doi.org/10.1091/mbc.E04-02-0147
  7. ↑ Meiling-Wesse K, Barth H, Voss C, Eskelinen EL, Epple UD, Thumm M. Atg21 is required for effective recruitment of Atg8 to the preautophagosomal structure during the Cvt pathway. J Biol Chem. 2004 Sep 3;279(36):37741-50. doi: 10.1074/jbc.M401066200. Epub 2004 , Jun 11. PMID:15194695 doi:http://dx.doi.org/10.1074/jbc.M401066200
  8. ↑ Krick R, Tolstrup J, Appelles A, Henke S, Thumm M. The relevance of the phosphatidylinositolphosphat-binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy. FEBS Lett. 2006 Aug 21;580(19):4632-8. doi: 10.1016/j.febslet.2006.07.041. Epub, 2006 Jul 21. PMID:16876790 doi:http://dx.doi.org/10.1016/j.febslet.2006.07.041
  9. ↑ Efe JA, Botelho RJ, Emr SD. Atg18 regulates organelle morphology and Fab1 kinase activity independent of its membrane recruitment by phosphatidylinositol 3,5-bisphosphate. Mol Biol Cell. 2007 Nov;18(11):4232-44. Epub 2007 Aug 15. PMID:17699591 doi:http://dx.doi.org/E07-04-0301
  10. ↑ Obara K, Sekito T, Niimi K, Ohsumi Y. The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J Biol Chem. 2008 Aug 29;283(35):23972-80. doi: 10.1074/jbc.M803180200. Epub 2008, Jun 27. PMID:18586673 doi:http://dx.doi.org/10.1074/jbc.M803180200
  11. ↑ Krick R, Henke S, Tolstrup J, Thumm M. Dissecting the localization and function of Atg18, Atg21 and Ygr223c. Autophagy. 2008 Oct;4(7):896-910. doi: 10.4161/auto.6801. Epub 2008 Oct 18. PMID:18769150 doi:http://dx.doi.org/10.4161/auto.6801
  12. ↑ Jin N, Chow CY, Liu L, Zolov SN, Bronson R, Davisson M, Petersen JL, Zhang Y, Park S, Duex JE, Goldowitz D, Meisler MH, Weisman LS. VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse. EMBO J. 2008 Dec 17;27(24):3221-34. doi: 10.1038/emboj.2008.248. Epub 2008 Nov, 27. PMID:19037259 doi:http://dx.doi.org/10.1038/emboj.2008.248
  13. ↑ Nair U, Cao Y, Xie Z, Klionsky DJ. Roles of the lipid-binding motifs of Atg18 and Atg21 in the cytoplasm to vacuole targeting pathway and autophagy. J Biol Chem. 2010 Apr 9;285(15):11476-88. doi: 10.1074/jbc.M109.080374. Epub 2010, Feb 12. PMID:20154084 doi:http://dx.doi.org/10.1074/jbc.M109.080374
  14. ↑ Nair U, Thumm M, Klionsky DJ, Krick R. GFP-Atg8 protease protection as a tool to monitor autophagosome biogenesis. Autophagy. 2011 Dec;7(12):1546-50. doi: 10.4161/auto.7.12.18424. PMID:22108003 doi:http://dx.doi.org/10.4161/auto.7.12.18424
  15. ↑ Kobayashi T, Suzuki K, Ohsumi Y. Autophagosome formation can be achieved in the absence of Atg18 by expressing engineered PAS-targeted Atg2. FEBS Lett. 2012 Jul 30;586(16):2473-8. doi: 10.1016/j.febslet.2012.06.008. Epub, 2012 Jun 19. PMID:22728243 doi:http://dx.doi.org/10.1016/j.febslet.2012.06.008
  16. ↑ Zieger M, Mayer A. Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements. Mol Biol Cell. 2012 Sep;23(17):3438-49. doi: 10.1091/mbc.E12-05-0347. Epub 2012, Jul 11. PMID:22787281 doi:http://dx.doi.org/10.1091/mbc.E12-05-0347
  17. ↑ Papinski D, Kraft C. Atg1 kinase organizes autophagosome formation by phosphorylating Atg9. Autophagy. 2014 Jul;10(7):1338-40. doi: 10.4161/auto.28971. Epub 2014 Apr 28. PMID:24905091 doi:http://dx.doi.org/10.4161/auto.28971
  18. ↑ Lei Y, Tang D, Liao G, Xu L, Liu S, Chen Q, Li C, Duan J, Wang K, Wang J, Sun B, Li Z, Dai L, Cheng W, Qi S, Lu K. The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae. Cell Mol Life Sci. 2020 Aug 18. pii: 10.1007/s00018-020-03621-9. doi:, 10.1007/s00018-020-03621-9. PMID:32809042 doi:http://dx.doi.org/10.1007/s00018-020-03621-9

6kyb, resolution 2.80Å

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