281 – Aminopeptidase I

Publisher Summary This chapter discusses the activity, specificity and structural chemistry of aminopeptidase I (APE I). The structure of the APE I gene encoding aminopeptidase I have been described. The precursor form contains an N-terminal 45 amino acid propeptide with an unusual helix-turn-helix structure and lacks a consensus signal sequence. The precursor is not glycosylated, remains in the cytoplasm and does not enter the secretory pathway; instead, the sorting signal within the predicted first a helix directs it to the vacuole. Transcription of APE I gene is regulated by the growth phase and by the carbon source used for yeast growth, responding to carbon catabolite repression. An upstream activating element consisting of at most 18 bp has been shown to be involved in carbon repression, and to bind a protein of 78 kDa and a heterodimer of 48 kDa. Transport of aminopeptidase I follows the nonclassical cytosolic vesicle transport pathway. The cytosolic preproenzyme dodecamerizes and is enclosed in a double membrane vesicle that goes to the vacuole and fuses with it, releasing a single-membrane autophagic body into the vacuole. It is found that degradation of the membrane and removal of the propeptide yield active aminopeptidase I.