| Structural highlights
Function
ATG19_YEAST Cargo-receptor protein involved in the cytoplasm to vacuole transport (Cvt) and in autophagy. Recognizes cargo proteins, such as APE4, LAP3, LAP4 and AMS1 and delivers them to the pre-autophagosomal structure for eventual engulfment by the autophagosome and targeting to the vacuole. Involved in the organization of the preautophagosomal structure (PAS). ATG19 association with cargo protein is required to localize ATG11 to the PAS. Also involved in endoplasmic reticulum-specific autophagic process, in selective removal of ER-associated degradation (ERAD) substrates, and is essential for the survival of cells subjected to severe ER stress. Plays also a role in regulation of filamentous growth.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]
Publication Abstract from PubMed
In the yeast Saccharomyces cerevisiae, a precursor form of aminopeptidase I (prApe1) and alpha-mannosidase (Ams1) are selectively transported to the vacuole through the cytoplasm-to-vacuole targeting pathway under vegetative conditions and through autophagy under starvation conditions. Atg19 plays a central role in these processes by linking Ams1 and prApe1 to Atg8 and Atg11. However, little is known about the molecular mechanisms of cargo recognition by Atg19. Here, we report structural and functional analyses of Atg19 and its paralog, Atg34. A protease-resistant domain was identified in the C-terminal region of Atg19, which was also conserved in Atg34. In vitro pulldown assays showed that the C-terminal domains of both Atg19 and Atg34 are responsible for Ams1 binding; these domains are hereafter referred to as Ams1-binding domains (ABDs). The transport of Ams1, but not prApe1, was blocked in atg19Deltaatg34Delta cells expressing Atg19(DeltaABD), indicating that ABD is specifically required for Ams1 transport. We then determined the solution structures of the ABDs of Atg19 and Atg34 using NMR spectroscopy. Both ABD structures have a canonical immunoglobulin fold consisting of eight beta-strands with highly conserved loops clustered at one side of the fold. These facts, together with the results of a mutational analysis, suggest that ABD recognizes Ams1 using these conserved loops.
Selective transport of alpha-mannosidase by autophagic pathways: structural basis for cargo recognition by Atg19 and Atg34.,Watanabe Y, Noda NN, Kumeta H, Suzuki K, Ohsumi Y, Inagaki F J Biol Chem. 2010 Sep 24;285(39):30026-33. Epub 2010 Jul 21. PMID:20659891[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ Scott SV, Guan J, Hutchins MU, Kim J, Klionsky DJ. Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway. Mol Cell. 2001 Jun;7(6):1131-41. PMID:11430817
- ↑ Suzuki K, Kamada Y, Ohsumi Y. Studies of cargo delivery to the vacuole mediated by autophagosomes in Saccharomyces cerevisiae. Dev Cell. 2002 Dec;3(6):815-24. PMID:12479807
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- ↑ Yorimitsu T, Klionsky DJ. Atg11 links cargo to the vesicle-forming machinery in the cytoplasm to vacuole targeting pathway. Mol Biol Cell. 2005 Apr;16(4):1593-605. Epub 2005 Jan 19. PMID:15659643 doi:http://dx.doi.org/10.1091/mbc.E04-11-1035
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- ↑ Mazon MJ, Eraso P, Portillo F. Efficient degradation of misfolded mutant Pma1 by endoplasmic reticulum-associated degradation requires Atg19 and the Cvt/autophagy pathway. Mol Microbiol. 2007 Feb;63(4):1069-77. PMID:17238920 doi:http://dx.doi.org/10.1111/j.1365-2958.2006.05580.x
- ↑ Kageyama T, Suzuki K, Ohsumi Y. Lap3 is a selective target of autophagy in yeast, Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2009 Jan 16;378(3):551-7. doi:, 10.1016/j.bbrc.2008.11.084. Epub 2008 Dec 4. PMID:19061865 doi:http://dx.doi.org/10.1016/j.bbrc.2008.11.084
- ↑ Kario E, Amar N, Elazar Z, Navon A. A new autophagy-related checkpoint in the degradation of an ERAD-M target. J Biol Chem. 2011 Apr 1;286(13):11479-91. doi: 10.1074/jbc.M110.177618. Epub 2011, Jan 12. PMID:21228276 doi:http://dx.doi.org/10.1074/jbc.M110.177618
- ↑ Noda NN, Kumeta H, Nakatogawa H, Satoo K, Adachi W, Ishii J, Fujioka Y, Ohsumi Y, Inagaki F. Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells. 2008 Oct 22. PMID:19021777 doi:GTC1238
- ↑ Watanabe Y, Noda NN, Kumeta H, Suzuki K, Ohsumi Y, Inagaki F. Selective transport of alpha-mannosidase by autophagic pathways: structural basis for cargo recognition by Atg19 and Atg34. J Biol Chem. 2010 Sep 24;285(39):30026-33. Epub 2010 Jul 21. PMID:20659891 doi:http://dx.doi.org/10.1074/jbc.M110.143545
- ↑ Watanabe Y, Noda NN, Kumeta H, Suzuki K, Ohsumi Y, Inagaki F. Selective transport of alpha-mannosidase by autophagic pathways: structural basis for cargo recognition by Atg19 and Atg34. J Biol Chem. 2010 Sep 24;285(39):30026-33. Epub 2010 Jul 21. PMID:20659891 doi:http://dx.doi.org/10.1074/jbc.M110.143545
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