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Journal article

Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase

Authors list: Tikkanen, Ritva; Peltola, Minna; Oinonen, Carita; Rouvinen, Juha; Peltonen, Leena

Publication year: 1997

Pages: 6684-6693

Journal: The EMBO Journal

Volume number: 16

Issue number: 22

ISSN: 0261-4189

DOI Link: https://doi.org/10.1093/emboj/16.22.6684

Publisher: EMBO Press

Abstract:
Lysosomal targeting of soluble lysosomal hydrolases is mediated by mannose 6-phosphate receptors, which recognize and bind mannose 6-phosphate residues in the oligosaccharide chains of proteins destined for delivery to lysosomes, This recognition marker is generated by the sequential action of two enzymes, the first of which, UDP-N-acetylglucosamine phosphotransferase, recognizes lysosomal enzymes on the basis of a structural determinant in their polypeptide chains, This recognition event is a key step in lysosomal targeting of soluble proteins, but the exact nature of the recognition determinant is not well understood, In this study we have characterized the phosphotransferase recognition signals of human lysosomal aspartylglucosaminidase (AGA) using transient expression of polypeptides carrying targeted amino acid substitutions, We found that three lysine residues and a tyrosine residing in three spatially distinct regions of the AGA polypeptide are necessary for phosphorylation of the oligosaccharides. Two of the lysines are especially important for the lysosomal targeting efficiency of AGA, which seems to be mostly dictated by the degree of phosphorylation of the a subunit oligosaccharide, On the basis of the results of this and previous studies we suggest a general model for recognition of lysosomal enzymes by the phosphotransferase.

Authors/Editors

- Uni.-Prof. Dr. Ritva Tikkanen

Citation Styles

Harvard Citation style: Tikkanen, R., Peltola, M., Oinonen, C., Rouvinen, J. and Peltonen, L. (1997) Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase, The EMBO Journal, 16(22), pp. 6684-6693. https://doi.org/10.1093/emboj/16.22.6684

APA Citation style: Tikkanen, R., Peltola, M., Oinonen, C., Rouvinen, J., & Peltonen, L. (1997). Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase. The EMBO Journal. 16(22), 6684-6693. https://doi.org/10.1093/emboj/16.22.6684