Structural highlightsFunction[ATGA1_HUMAN] Autophagy factor required for autophagosome formation. Stabilizes ATG13, protecting it from proteasomal degradation.[1] [2] [ATG13_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.[3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
The ULK1 complex, consisting of the ULK1 protein kinase itself, FIP200, Atg13, and Atg101, controls the initiation of autophagy in animals. We determined the structure of the complex of the human Atg13 HORMA (Hop1, Rev7, Mad2) domain in complex with the full-length HORMA domain-only protein Atg101. The two HORMA domains assemble with an architecture conserved in the Mad2 conformational heterodimer and the S. pombe Atg13-Atg101 HORMA complex. The WF finger motif that is essential for function in human Atg101 is sequestered in a hydrophobic pocket, suggesting that the exposure of this motif is regulated. Benzamidine molecules from the crystallization solution mark two hydrophobic pockets that are conserved in, and unique to, animals, and are suggestive of sites that could interact with other proteins. These features suggest that the activity of the animal Atg13-Atg101 subcomplex is regulated and that it is an interaction hub for multiple partners.
Structure of the Human Atg13-Atg101 HORMA Heterodimer: an Interaction Hub within the ULK1 Complex.,Qi S, Kim do J, Stjepanovic G, Hurley JH Structure. 2015 Oct 6;23(10):1848-57. doi: 10.1016/j.str.2015.07.011. Epub 2015, Aug 20. PMID:26299944[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Hosokawa N, Sasaki T, Iemura S, Natsume T, Hara T, Mizushima N. Atg101, a novel mammalian autophagy protein interacting with Atg13. Autophagy. 2009 Oct;5(7):973-9. Epub 2009 Oct 18. PMID:19597335
- ↑ 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
- ↑ Qi S, Kim do J, Stjepanovic G, Hurley JH. Structure of the Human Atg13-Atg101 HORMA Heterodimer: an Interaction Hub within the ULK1 Complex. Structure. 2015 Oct 6;23(10):1848-57. doi: 10.1016/j.str.2015.07.011. Epub 2015, Aug 20. PMID:26299944 doi:http://dx.doi.org/10.1016/j.str.2015.07.011
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