Novel Chaperone-Like pro-Sequences allow Secretion of Recombinant Human Insulin-Like Growth Factor-1 from Yeast

Abstract

Protein secretion in eukaryotes is defined as a process where polypeptides, newly translated on ribosomes, undergo translocation across the membrane of the rough endoplasmic reticulum (ER) and then, through vesicular packaging, is ferried through the Golgi cisternae on its route to the periplasmic space (Rothman and Orci, 1992). All secretory proteins need transient N-terminal signals for targeting to the ER (Walter and Lingappa, 1986). The signals are embodied by short peptides (15 to 30 amino acid long), the core of which consists of only hydrophobic residues (von Heijne, 1985). In most cases, the enzyme signal peptidase cleaves the signal peptide after it has engaged the nascent protein in the translocation machinery (Walter and Lingappa, 1986). The resultant mature protein is then free to fold into an appropriate conformation, necessary for the activity of the molecule.