| Structural highlights
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
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- ↑ 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
- ↑ 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
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- ↑ 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
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- ↑ 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
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- ↑ 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
- ↑ 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
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- ↑ 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
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