9BGG
Structure of a hyperactive S1S3 truncation of the human GlcNAc-1-phosphotransferase
Summary for 9BGG
| Entry DOI | 10.2210/pdb9bgg/pdb |
| Related | 9bgf |
| EMDB information | 44512 |
| Descriptor | highly active truncation of GlcNAc-1-phosphotransferase, S1S3,N-acetylglucosamine-1-phosphotransferase subunit beta, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total) |
| Functional Keywords | glcnac-1-phosphotransferase, lysosomal hydrolases, mannose 6-phosphate trafficking pathway, transferase |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 2 |
| Total formula weight | 118223.50 |
| Authors | |
| Primary citation | Li, H.,Doray, B.,Jennings, B.C.,Lee, W.S.,Liu, L.,Kornfeld, S.,Li, H. Structure of a truncated human GlcNAc-1-phosphotransferase variant reveals the basis for its hyperactivity. J.Biol.Chem., 300:107706-107706, 2024 Cited by PubMed Abstract: Mutations that cause loss of function of GlcNAc-1-phosphotransferase (PTase) lead to the lysosomal storage disorder mucolipidosis II. PTase is the key enzyme of the mannose 6-phosphate (M6P) targeting system that is responsible for tagging lysosomal hydrolases with the M6P moiety for their delivery to the lysosome. We had previously generated a truncated hyperactive form of PTase termed S1S3 which was shown to notably increase the phosphorylation level of secreted lysosomal enzymes and enhance their uptake by cells. Here, we report the 3.4 Å cryo-EM structure of soluble S1S3 lacking both transmembrane domains and cytosolic tails. The structure reveals a high degree of conservation of the catalytic core to full-length PTase. In this dimeric structure, the EF-hand of one protomer is observed interacting with the conserved region four of the other. In addition, we present a high-quality EM 3D map of the UDP-GlcNAc bound form of the full-length soluble protein showing the key molecular interactions between the nucleotide sugar donor and side chain amino acids of the protein. Finally, although the domain organization of S1S3 is very similar to that of the Drosophila melanogaster (fruit fly) PTase homolog, we establish that the latter does not act on lysosomal hydrolases. PubMed: 39178950DOI: 10.1016/j.jbc.2024.107706 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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