Autophagin

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Schematic drawing of Atg4b. The color codes for the secondary structure elements are: alpha-helix, cyan; beta strands, magenta; loops, salmon. The active site residues Y54, C74, W142, R229, D278 and H280 are shown in ball-and stick representation. The coordinates and structure factors have been deposited in the RCSB PDB (accession code 2D1I).

Autophagin-1 (Atg4/Apg4) is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8/Apg8/Aut7, a reaction essential for its lipidation during autophagy^[1]. Human Atg4 homologues cleave the carboxyl termini of the three human Atg8 homologues, microtubule-associated protein light chain 3 (LC3), GABARAP, and GATE-16 ^[2].

The rapid advancement in our understanding of the mechanisms and regulation of autophagy has placed this process in the center of current research in major human disorders^[3]. The future challenge is to develop easy methods to separately manipulate the activity of each of the autophagic pathways. This would allow to further understand their contribution to disease such as cancer, neurodegeneration, infectious disease, muscular disorders and possibly will provide therapeutic tools.

[edit] References

1. ^ Development by self-digestion: molecular mechanisms and biological functions of autophagy by Levine B, Klionsky DJ. in Dev Cell. 2004 Apr;6(4):463-77. Review.
2. ^ HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates byTanida I, Sou YS, Ezaki J, Minematsu-Ikeguchi N, Ueno T, Kominami E. in J Biol Chem. 2004 Aug 27;279(35):36268-76
3. ^ Autophagy: in sickness and in health by Cuervo AM. in Trends Cell Biol. 2004 Feb;14(2):70-7.