Lysine-based structure in the proregion of procathepsin L is the recognition site for mannose phosphorylation.
The recognition of lysosomal enzymes by UDP-GlcNAc: lysosomal-enzyme GlcNAc-1-phosphotransferase (phosphotransferase) is mediated by a protein structure on lysosomal enzymes. It has been previously demonstrated that lysine residues are required for phosphorylation of procathepsin L and are a common feature of the site on many lysosomal proteins. In this work, the procathepsin L recognition structure was further defined by identification of the region of the protein containing the structure and the critical lysine residues involved. Removal of the cathepsin L propeptide by low pH-induced autocatalytic processing abolished phosphorylation. The addition of either the purified propeptide or a glutathione S-transferase-propeptide fusion protein to the processed protein restored phosphorylation. Mutagenesis of individual lysine residues demonstrated that two propeptide lysine residues (Lys-54 and Lys-99) were required for efficient phosphorylation of procathepsin L. By comparison of the phosphorylation rates of procathepsin L, lysine-modified procathepsin L, and the procathepsin L oligosaccharide, lysine residues were shown to account for most, if not all, of the protein-dependent interaction. On this basis, it is concluded that the proregion lysine residues are the major elements of the procathepsin L recognition site. In addition, lysine residues in cathepsin D were shown to be as important for phosphorylation as those in procathepsin L, supporting a general model of the recognition site as a specific three-dimensional arrangement of lysine residues exposed on the surface of lysosomal proteins.
Published In/Presented At
Cuozzo, J. W., Tao, K., Wu, Q. L., Young, W., & Sahagian, G. G. (1995). Lysine-based structure in the proregion of procathepsin L is the recognition site for mannose phosphorylation. The Journal of biological chemistry, 270(26), 15611–15619. https://doi.org/10.1074/jbc.270.26.15611
Diagnosis | Medicine and Health Sciences | Other Analytical, Diagnostic and Therapeutic Techniques and Equipment | Radiology
Department of Radiology and Diagnostic Medical Imaging