Structural highlightsFunctionATG13_HUMAN Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.[1] [2] [3] [4] [5] [6] GBRAP_HUMAN May play a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in apoptosis. Involved in autophagy (By similarity).[7]
Publication Abstract from PubMed
Autophagy is an essential recycling and quality control pathway. Mammalian ATG8 proteins drive autophagosome formation and selective removal of protein aggregates and organelles by recruiting autophagy receptors and adaptors that contain a LC3-interacting region (LIR) motif. LIR motifs can be highly selective for ATG8 subfamily proteins (LC3s/GABARAPs), however the molecular determinants regulating these selective interactions remain elusive. Here we show that residues within the core LIR motif and adjacent C-terminal region as well as ATG8 subfamily-specific residues in the LIR docking site are critical for binding of receptors and adaptors to GABARAPs. Moreover, rendering GABARAP more LC3B-like impairs autophagy receptor degradation. Modulating LIR binding specificity of the centriolar satellite protein PCM1, implicated in autophagy and centrosomal function, alters its dynamics in cells. Our data provides new mechanistic insight into how selective binding of LIR motifs to GABARAPs is achieved, and elucidate the overlapping and distinct functions of ATG8 subfamily proteins.
Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins.,Wirth M, Zhang W, Razi M, Nyoni L, Joshi D, O'Reilly N, Johansen T, Tooze SA, Mouilleron S Nat Commun. 2019 May 3;10(1):2055. doi: 10.1038/s41467-019-10059-6. PMID:31053714[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See AlsoReferences
- ↑ Mercer CA, Kaliappan A, Dennis PB. A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy. 2009 Jul;5(5):649-62. Epub 2009 Jul 20. PMID:19287211
- ↑ Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, Guan JL, Oshiro N, Mizushima N. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 2009 Apr;20(7):1981-91. doi: 10.1091/mbc.E08-12-1248. Epub 2009, Feb 11. PMID:19211835 doi:http://dx.doi.org/10.1091/mbc.E08-12-1248
- ↑ Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009 Apr;20(7):1992-2003. doi: 10.1091/mbc.E08-12-1249. Epub 2009 , Feb 18. PMID:19225151 doi:http://dx.doi.org/10.1091/mbc.E08-12-1249
- ↑ Joo JH, Dorsey FC, Joshi A, Hennessy-Walters KM, Rose KL, McCastlain K, Zhang J, Iyengar R, Jung CH, Suen DF, Steeves MA, Yang CY, Prater SM, Kim DH, Thompson CB, Youle RJ, Ney PA, Cleveland JL, Kundu M. Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy. Mol Cell. 2011 Aug 19;43(4):572-85. doi: 10.1016/j.molcel.2011.06.018. PMID:21855797 doi:http://dx.doi.org/10.1016/j.molcel.2011.06.018
- ↑ Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol. 2009 Jan;29(1):157-71. doi: 10.1128/MCB.01082-08. Epub 2008 Oct, 20. PMID:18936157 doi:http://dx.doi.org/10.1128/MCB.01082-08
- ↑ Jung CH, Seo M, Otto NM, Kim DH. ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy. 2011 Oct;7(10):1212-21. doi: 10.4161/auto.7.10.16660. Epub 2011 Oct 1. PMID:21795849 doi:http://dx.doi.org/10.4161/auto.7.10.16660
- ↑ Lee JH, Rho SB, Chun T. GABAA receptor-associated protein (GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47). Biotechnol Lett. 2005 May;27(9):623-8. PMID:15977068 doi:http://dx.doi.org/10.1007/s10529-005-3628-2
- ↑ Wirth M, Zhang W, Razi M, Nyoni L, Joshi D, O'Reilly N, Johansen T, Tooze SA, Mouilleron S. Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins. Nat Commun. 2019 May 3;10(1):2055. doi: 10.1038/s41467-019-10059-6. PMID:31053714 doi:http://dx.doi.org/10.1038/s41467-019-10059-6
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