Autophagy-related protein

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Function

Autophagy-related proteins (Atg) function in autophagosome formation from the pre-autophagosomal structure (PAS). The phagosomes perform protein degradation under starvation. Autophagy is the process of forming a vacuole around proteins or nucleic acids destined to be broken down. This vacuole is a double membrane enclosure called phagophore. Atgs have non-autophagic functions as well as they are involved in cell survival and apoptosis.[1] So far 34 Atgs have been identified in yeast.

  • Atg1, 6, 14 are involved in the formation of the phagophore.
  • Atg2 is essential for autophagosome formation[2].
  • Atg3 catalyzes the conjugation of Atg8 and phosphatidylethanolamine. This conjugation is essential for autophagosome formation[3].
  • Atg4, 5, 7, 10, 16 are involved in the maturation of the phagophore.
  • Atg8 is structurally similar to ubiquitin. It is a targeting factor in cytoplasm-to-vacuole transport of proteins such as aminopeptidase and a-mannosidase. Microtubule-associated protein light chain 3 LC3 is a mammalian Atg8[4].
  • Atg9 mediates autophagosomal membrane expansion[5].
  • Atg11 is essential for selective autophagy[6].
  • Atg12 is involved in the elongation of the phagophore.
  • Atg13, 17 are PAS scaffold proteins.
  • Atg18 forms a complex with Atg2 which tethers membranes to the ER for autophagosome formation[7].
  • Atg101 is believed to protect Atg13 from proteasomal degradation.

Structural highlights

(PDB code 3vh3). in yeast Atg7 C-terminal domain.[8]

3D Structures of autophagy-related protein

Autophagy-related protein 3D structures


Yeast Atg7 C terminal (green) complex with Atg8 (magenta) and Zn+2 ion (grey) (PDB code 3vh3)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Shibutani ST, Saitoh T, Nowag H, Munz C, Yoshimori T. Autophagy and autophagy-related proteins in the immune system. Nat Immunol. 2015 Sep 18;16(10):1014-24. doi: 10.1038/ni.3273. PMID:26382870 doi:http://dx.doi.org/10.1038/ni.3273
  2. ↑ Velikkakath AK, Nishimura T, Oita E, Ishihara N, Mizushima N. Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets. Mol Biol Cell. 2012 Mar;23(5):896-909. doi: 10.1091/mbc.E11-09-0785. Epub 2012, Jan 4. PMID:22219374 doi:http://dx.doi.org/10.1091/mbc.E11-09-0785
  3. ↑ Ngu M, Hirata E, Suzuki K. Visualization of Atg3 during autophagosome formation in Saccharomyces cerevisiae. J Biol Chem. 2015 Mar 27;290(13):8146-53. doi: 10.1074/jbc.M114.626952. Epub 2015, Feb 2. PMID:25645919 doi:http://dx.doi.org/10.1074/jbc.M114.626952
  4. ↑ Lystad AH, Simonsen A. Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery. Cells. 2019 Aug 25;8(9). pii: cells8090973. doi: 10.3390/cells8090973. PMID:31450711 doi:http://dx.doi.org/10.3390/cells8090973
  5. ↑ Matoba K, Kotani T, Tsutsumi A, Tsuji T, Mori T, Noshiro D, Sugita Y, Nomura N, Iwata S, Ohsumi Y, Fujimoto T, Nakatogawa H, Kikkawa M, Noda NN. Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion. Nat Struct Mol Biol. 2020 Oct 26. pii: 10.1038/s41594-020-00518-w. doi:, 10.1038/s41594-020-00518-w. PMID:33106658 doi:http://dx.doi.org/10.1038/s41594-020-00518-w
  6. ↑ Zientara-Rytter K, Subramani S. Mechanistic Insights into the Role of Atg11 in Selective Autophagy. J Mol Biol. 2020 Jan 3;432(1):104-122. doi: 10.1016/j.jmb.2019.06.017. Epub 2019 , Jun 22. PMID:31238043 doi:http://dx.doi.org/10.1016/j.jmb.2019.06.017
  7. ↑ Kotani T, Kirisako H, Koizumi M, Ohsumi Y, Nakatogawa H. The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation. Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10363-10368. doi:, 10.1073/pnas.1806727115. Epub 2018 Sep 25. PMID:30254161 doi:http://dx.doi.org/10.1073/pnas.1806727115
  8. ↑ Noda NN, Satoo K, Fujioka Y, Kumeta H, Ogura K, Nakatogawa H, Ohsumi Y, Inagaki F. Structural basis of Atg8 activation by a homodimeric E1, Atg7. Mol Cell. 2011 Nov 4;44(3):462-75. PMID:22055191 doi:10.1016/j.molcel.2011.08.035

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