The signal sequence of ovalbumin is located near the NH2 terminus.

Abstract Ovalbumin, unlike other secretory proteins, is synthesized and secreted without cleavage of a hydrophobic signal peptide. Kinetic experiments were performed in a cell-free translation system to measure the minimum size of ovalbumin nascent chains required for binding of both the nascent chain and the corresponding mRNA to microsomal membranes derived from dog pancreas. Results of these experiments revealed that 50 to 60 amino acid residues are sufficient to bind ovalbumin-synthesizing polysomes to membranes in vitro. When microsomes with associated polysomes were isolated from chick oviduct, nascent ovalbumin chains longer than 50 residues were protected from proteolysis as long as the membranes remained intact, suggesting that the polypeptides were sequestered by the endoplasmic reticulum. We conclude that the functional signal for membrane translocation of ovalbumin becomes accessible when the nascent chain is 50 to 60 residues long. We speculate that the hydrophobic sequence which lies between residues 25 and 45 folds back on the preceding residues to form an amphipathic hairpin structure which is the signal element recognized by the membrane.