In molecular biology, autophagy related 3 (Atg3) is the E2 enzyme for the LC3 lipidation process.[1] It is essential for autophagy. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place.[2]
Atg3 catalyses the conjugation of Atg8 and phosphatidylethanolamine (PE). Atg3 has an alpha/beta-fold, and its core region is topologically similar to canonical E2 enzymes. Atg3 has two regions inserted in the core region and another with a long alpha-helical structure that protrudes from the core region as far as 30 A.[3] It interacts with atg8 through an intermediate thioester bond between Cys-288 and the C-terminal Gly of atg8. It also interacts with the C-terminal region of the E1-like atg7 enzyme.
Autophagocytosis is a starvation-induced process responsible for transport of cytoplasmic proteins to the lysosome/vacuole. Atg3 is a ubiquitin like modifier that is topologically similar to the canonical E2 enzyme.[4] It catalyses the conjugation of Atg8 and phosphatidylethanolamine.[5]
Atg3 consists of three domains, an N-terminal domain, a catalytic domain and a C-terminal domain. The catalytic domain contains a cysteine residue within an HPC motif, this is the putative active-site residue for recognition of the Apg5 subunit of the autophagosome complex.[6] The small C-terminal domain is likely to be a distinct binding region for the stability of the autophagosome complex.[7] It carries a highly characteristic conserved FLKF sequence motif.
References
- ^ Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T (May 2008). "The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy". Mol. Biol. Cell. 19 (5): 2092–100. doi:10.1091/mbc.E07-12-1257. PMC 2366860. PMID 18321988.
- ^ Noda T, Fujita N, Yoshimori T (May 2008). "The Ubi brothers reunited". Autophagy. 4 (4): 540–1. doi:10.4161/auto.5973. PMID 18398292.
- ^ Yamada Y, Suzuki NN, Hanada T, Ichimura Y, Kumeta H, Fujioka Y, Ohsumi Y, Inagaki F (March 2007). "The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates Atg8 lipidation". J. Biol. Chem. 282 (11): 8036–43. doi:10.1074/jbc.M611473200. PMID 17227760.
- ^ Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E (April 2002). "Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p". J. Biol. Chem. 277 (16): 13739–44. doi:10.1074/jbc.M200385200. PMID 11825910.
- ^ Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M (February 1997). "AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae". J. Bacteriol. 179 (4): 1068–76. doi:10.1128/jb.179.4.1068-1076.1997. PMC 178799. PMID 9023185.
- ^ Mizushima N, Yoshimori T, Ohsumi Y (December 2002). "Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid method". FEBS Lett. 532 (3): 450–4. doi:10.1016/S0014-5793(02)03739-0. PMID 12482611. S2CID 37247321.
- ^ Mizushima N, Yoshimori T, Ohsumi Y (May 2003). "Role of the Apg12 conjugation system in mammalian autophagy". Int. J. Biochem. Cell Biol. 35 (5): 553–61. doi:10.1016/S1357-2725(02)00343-6. PMID 12672448.
This page was last edited on 1 December 2023, at 06:21