Journal article

Publication year: 1996

Pages: 21340-21344

Journal: Journal of Biological Chemistry

Volume number: 271

Issue number: 35

ISSN: 0021-9258

DOI Link: https://doi.org/10.1074/jbc.271.35.21340

Publisher: Elsevier

Abstract: 
Aspartylglucosaminidase (AGA) is a lysosomal enzyme involved in the degradation of N-linked glycoproteins in lysosomes. AGA is synthesized as an inactive precursor molecule, which is rapidly activated in the endoplasmic reticulum by a proteolytic cleavage into alpha- and beta-subunits. We have recently determined the three-dimensional structure of AGA and shown that it is a globular molecule with a heterotetrameric (alpha beta)(2) structure, On the basis of structural and functional analyses, AGA seems to be the first mammalian protein belonging to a newly described protein family, the N-tepminal nucleophile hydrolases, Because the activation of the prokaryotic members of the N-terminal nucleophile hydrolase family seems to be triggered by the assembly of the subunits, we have studied the initial folding and oligomerization of AGA and provide evidence that dimerization of two precursor molecules in the endoplasmic reticulum is a prerequisite for the activation of AGA To gain further information on the structural determinants influencing the early folding of AGA, we used site-specific mutagenesis of cysteine residues to define the role of intrachain disulfide bridges in the folding and activation of the enzyme. The N-terminal disulfide bridges in both the alpha- and beta-subunits seem to have only a stabilizing role, whereas the C-terminal disulfide bridge in both subunits evidently plays an important role in the early folding and activation of AGA.

Harvard Citation style: Riikonen, A., Rouvinen, J., Tikkanen, R., Julkunen, I., Peltonen, L. and Jalanko, A. (1996) Primary folding of aspartylglucosaminidase. Significance of disulfide bridges and evidence of early multimerization, Journal of Biological Chemistry, 271(35), pp. 21340-21344. https://doi.org/10.1074/jbc.271.35.21340

APA Citation style: Riikonen, A., Rouvinen, J., Tikkanen, R., Julkunen, I., Peltonen, L., & Jalanko, A. (1996). Primary folding of aspartylglucosaminidase. Significance of disulfide bridges and evidence of early multimerization. Journal of Biological Chemistry. 271(35), 21340-21344. https://doi.org/10.1074/jbc.271.35.21340