Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Tyrosinase is the key enzyme of melanin biosynthesis. It is a multiply glycosylated metalloenzyme, which has a long maturation time making it an ideal in vivo model system to probe protein folding and metal loading events. The use of NB-DNJ, an alpha-glucosidase I and II inhibitor has allowed us to dissect these processes. Here we show that tyrosinase folds through several inactive intermediates, at least two of which are recognised by the ER chaperone, calnexin. If the association with calnexin is prevented, more rapid folding occurs, the resulting protein fails to bind copper and is inactive. If dissociation from calnexin is inhibited, folding is prevented; the protein does not go through the normal secretory pathway and is targeted for degradation. Thus, tyrosinase folds off calnexin, giving alpha-glucosidase II a critical role, but the association with calnexin is essential to promote the correct folding which enables it to acquire copper.

Original publication

DOI

10.1006/bbrc.1999.1030

Type

Journal article

Journal

Biochem Biophys Res Commun

Publication Date

11/08/1999

Volume

261

Pages

720 - 725

Keywords

Animals, Calcium-Binding Proteins, Calnexin, Copper, Melanoma, Experimental, Melanosomes, Mice, Monophenol Monooxygenase, Protein Folding, Tumor Cells, Cultured, alpha-Glucosidases