High impact information on ATG5

• The carboxy-terminal glycine residue of Apg12, a 186-amino-acid protein, is conjugated to a lysine at residue 149 of Apg5, a 294-amino-acid protein [1].
• We recently found in yeast that a novel ubiquitin-like system, the Apg12-Apg5 conjugation system, is essential for autophagy [2].
• Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells [2].
• Here we show that mouse Apg12-Apg5 conjugate localizes to the isolation membranes in mouse embryonic stem cells [2].
• Moreover, the coiled-coil domain of Apg16p mediates self-multimerization that leads to cross-linking of Apg5p molecules and formation of a stable protein complex [3].

Biological context of ATG5

• Similar to plants missing ATG7, those missing ATG5 display early senescence and are hypersensitive to either nitrogen or carbon starvation, which is accompanied by a more rapid loss of organellar and cytoplasmic proteins [4].
• We have generated mutations in apg5 and apg7 that produce defects typically associated with an abrogation of autophagy [5].
• The lack of apparent phenotype in rich medium suggests that APG5 function is required only under nutrient starvation condition, however, Northern blot analysis showed that its expression levels remained unchanged after nutrient depletion [6].

Anatomical context of ATG5

• The in vivo interaction of mApg12 with mApg10 in HeLa cells suggests that mApg10 is an Apg12-conjugating enzyme, likely serving as an Apg5-recognition molecule in the Apg12 system [7].
• Here we show that the Apg12-Apg5 conjugate and Apg16 form a approximately 350-kDa complex in the cytosol [8].

Associations of ATG5 with chemical compounds

• Two conjugation reactions related to ubiquitination are essential for autophagy: Apg12p conjugation to Apg5p, and Apg8p conjugation to the lipid phosphatidylethanolamine [5].
• The C-terminal glycine of a novel modifier protein, Apg12p, is conjugated to a lysine residue of Apg5p via an isopeptide bond [9].
• One of the APG gene products, Apg12p, is covalently attached to Apg5p via the C-terminal Gly of Apg12p as in the case of ubiquitylation, and this conjugation is essential for autophagy [10].

Physical interactions of ATG5

• This process requires a ubiquitin-like protein conjugation system, in which Apg12 is covalently bound to Apg5 [8].
• Saccharomyces cerevisiae Atg5 in complex with the N-terminal regions of Atg16 was expressed, purified and crystallized in four crystal forms [11].

Other interactions of ATG5

• We show that the Apg5-Apg12 conjugation system is conserved in Dictyostelium [5].
• By analyzing the stage of API import that is blocked in the apg5(ts) mutant, we have determined that Apg5p is involved in the sequestration step and is required for vesicle formation and/or completion [12].
• The attachment of Apg12p, a modifier with no significant similarity to ubiquitin, to Apg5p is crucial for autophagy in yeast [13].
• Degradation of mitochondrial proteins, followed by Western blot analysis, did not occur in mutant strains carrying null mutations of the vacuolar protease Pep4p, the autophagy-specific protein Atg5p, and Uth1p [14].

Analytical, diagnostic and therapeutic context of ATG5

• Expression, purification and crystallization of the Atg5-Atg16 complex essential for autophagy [11].

References