Höfundar:
Valgerður Hjaltalín, Vivian Pogenberg, Kevin Ostacolo, Arnar Pálsson, Margrét Helga Ögmundsdóttir
Introduction
Autophagy is a highly conserved degradation pathway important for maintaining homeostasis in eukaryotic cells. The E1-like enzyme ATG7 belongs to a group of ATG proteins that mediate the autophagy process. Several autophagy independent functions of ATG7 have been described and studies have suggested a more important function of the protein in mammalian models. We set out to investigate the evolutionary history of ATG7. We wanted to know whether a new functional region had emerged in the history of eukaryotes that could harbor a novel function.
Methods
Bioinformatical methods were applied to study the evolution of ATG7 from yeast to mammals. To address a putative mammalian specific function of ATG7, mouse embryonic fibroblasts (MEFs) with doxycycline inducible expression of different ATG7 constructs were generated.
Results
The study revealed a region of ATG7 that emerged early in vertebrates. Interestingly, this vertebrate specific region (VSR) is situated within the active domain of the protein and the most highly conserved domain of the E1-enzyme family. Structural models of ATG7 in various eukaryotic species predict that the VSR forms an intrinsically disordered loop that extends out from the protein, leaving it open to interactions with other macromolecules. Interestingly, MEFs expressing ATG7 lacking the VSR were unable to carry out its characterized function in autophagy.
Conclusions
While the role of the VSR remains to be elucidated, our data suggests that the region is important to the function of ATG7 in autophagy.