| Structural highlights
Disease
[A16L1_HUMAN] Crohn disease. Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
[ATG5_HUMAN] Involved in autophagy vesicles formation. Conjugation with ATG12 through an ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. The ATG12-ATG5 conjugate also regulates negatively the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Plays also a role in translation or delivery of incoming viral RNA to the translation apparatus. HCV utilizes ATG5 as a proviral factor during the onset of viral infection. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures; as well as in normal adipocyte differentiation.[1] [2] [3] [4] [5] [6] May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.[7] [8] [9] [10] [11] [12] [A16L1_HUMAN] Plays an essential role in autophagy: interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II.[13]
Publication Abstract from PubMed
Autophagy is a bulky catabolic process that responds to nutrient homeostasis and extracellular stress signals and is a conserved mechanism in all eukaryotes. When autophagy is induced, cellular components are sequestered within an autophagosome and finally degraded by subsequent fusion with a lysosome. During this process, the ATG12-ATG5 conjugate requires 2 different binding partners, ATG16L1 for autophagosome elongation and TECPR1 for lysosomal fusion. In our current study, we describe the crystal structures of human ATG5 in complex with an N-terminal domain of ATG16L1 as well as an internal AIR domain of TECPR1. Both binding partners exhibit a similar alpha-helical structure containing a conserved binding motif termed AFIM. Furthermore, we characterize the critical role of the C-terminal unstructured region of the AIR domain of TECPR1. These findings are further confirmed by biochemical and cell biological analyses. These results provide new insights into the molecular details of the autophagosome maturation process, from its elongation to its fusion with a lysosome.
Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners.,Kim JH, Hong SB, Lee JK, Han S, Roh KH, Lee KE, Kim YK, Choi EJ, Song HK Autophagy. 2015 Jan 2;11(1):75-87. doi: 10.4161/15548627.2014.984276. PMID:25484072[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Grand RJ, Milner AE, Mustoe T, Johnson GD, Owen D, Grant ML, Gregory CD. A novel protein expressed in mammalian cells undergoing apoptosis. Exp Cell Res. 1995 Jun;218(2):439-51. PMID:7796880 doi:http://dx.doi.org/S0014-4827(85)71177-9
- ↑ Tanida I, Nishitani T, Nemoto T, Ueno T, Kominami E. Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1164-70. PMID:12207896
- ↑ Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, Cho DH, Choi B, Lee H, Kim JH, Mizushima N, Oshumi Y, Jung YK. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem. 2005 May 27;280(21):20722-9. Epub 2005 Mar 18. PMID:15778222 doi:http://dx.doi.org/10.1074/jbc.M413934200
- ↑ Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, Ishii KJ, Kawai T, Akira S, Suzuki K, Okuda K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5. Epub 2007 Aug 20. PMID:17709747 doi:http://dx.doi.org/10.1073/pnas.0704014104
- ↑ Guevin C, Manna D, Belanger C, Konan KV, Mak P, Labonte P. Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection. Virology. 2010 Sep 15;405(1):1-7. doi: 10.1016/j.virol.2010.05.032. Epub 2010 Jun, 26. PMID:20580051 doi:http://dx.doi.org/10.1016/j.virol.2010.05.032
- ↑ Mai S, Muster B, Bereiter-Hahn J, Jendrach M. Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy. 2012 Jan;8(1):47-62. doi: 10.4161/auto.8.1.18174. Epub 2012 Jan 1. PMID:22170153 doi:http://dx.doi.org/10.4161/auto.8.1.18174
- ↑ Grand RJ, Milner AE, Mustoe T, Johnson GD, Owen D, Grant ML, Gregory CD. A novel protein expressed in mammalian cells undergoing apoptosis. Exp Cell Res. 1995 Jun;218(2):439-51. PMID:7796880 doi:http://dx.doi.org/S0014-4827(85)71177-9
- ↑ Tanida I, Nishitani T, Nemoto T, Ueno T, Kominami E. Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1164-70. PMID:12207896
- ↑ Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, Cho DH, Choi B, Lee H, Kim JH, Mizushima N, Oshumi Y, Jung YK. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem. 2005 May 27;280(21):20722-9. Epub 2005 Mar 18. PMID:15778222 doi:http://dx.doi.org/10.1074/jbc.M413934200
- ↑ Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, Ishii KJ, Kawai T, Akira S, Suzuki K, Okuda K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5. Epub 2007 Aug 20. PMID:17709747 doi:http://dx.doi.org/10.1073/pnas.0704014104
- ↑ Guevin C, Manna D, Belanger C, Konan KV, Mak P, Labonte P. Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection. Virology. 2010 Sep 15;405(1):1-7. doi: 10.1016/j.virol.2010.05.032. Epub 2010 Jun, 26. PMID:20580051 doi:http://dx.doi.org/10.1016/j.virol.2010.05.032
- ↑ Mai S, Muster B, Bereiter-Hahn J, Jendrach M. Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy. 2012 Jan;8(1):47-62. doi: 10.4161/auto.8.1.18174. Epub 2012 Jan 1. PMID:22170153 doi:http://dx.doi.org/10.4161/auto.8.1.18174
- ↑ Boada-Romero E, Letek M, Fleischer A, Pallauf K, Ramon-Barros C, Pimentel-Muinos FX. TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3. EMBO J. 2013 Feb 20;32(4):566-82. doi: 10.1038/emboj.2013.8. Epub 2013 Feb 1. PMID:23376921 doi:http://dx.doi.org/10.1038/emboj.2013.8
- ↑ Kim JH, Hong SB, Lee JK, Han S, Roh KH, Lee KE, Kim YK, Choi EJ, Song HK. Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners. Autophagy. 2015 Jan 2;11(1):75-87. doi: 10.4161/15548627.2014.984276. PMID:25484072 doi:http://dx.doi.org/10.4161/15548627.2014.984276
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