7KDV
Murine core lysosomal multienzyme complex (LMC) composed of acid beta-galactosidase (GLB1) and protective protein cathepsin A (PPCA, CTSA)
Summary for 7KDV
| Entry DOI | 10.2210/pdb7kdv/pdb |
| EMDB information | 22830 |
| Descriptor | Beta-galactosidase, Lysosomal protective protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | glycosidase, protease, lysosome, hydrolase |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 12 |
| Total formula weight | 759892.23 |
| Authors | Gorelik, A.,Illes, K.,Hasan, S.M.N.,Nagar, B.,Mazhab-Jafari, M.T. (deposition date: 2020-10-09, release date: 2021-03-17, Last modification date: 2024-11-13) |
| Primary citation | Gorelik, A.,Illes, K.,Hasan, S.M.N.,Nagar, B.,Mazhab-Jafari, M.T. Structure of the murine lysosomal multienzyme complex core. Sci Adv, 7:-, 2021 Cited by PubMed Abstract: The enzymes β-galactosidase (GLB1) and neuraminidase 1 (NEU1; sialidase 1) participate in the degradation of glycoproteins and glycolipids in the lysosome. To remain active and stable, they associate with PPCA [protective protein cathepsin A (CTSA)] into a high-molecular weight lysosomal multienzyme complex (LMC), of which several forms exist. Genetic defects in these three proteins cause the lysosomal storage diseases GM1-gangliosidosis/mucopolysaccharidosis IV type B, sialidosis, and galactosialidosis, respectively. To better understand the interactions between these enzymes, we determined the three-dimensional structure of the murine LMC core. This 0.8-MDa complex is composed of three GLB1 dimers and three CTSA dimers, adopting a triangular architecture maintained through six copies of a unique GLB1-CTSA polar interface. Mutations in this contact surface that occur in GM1-gangliosidosis prevent formation of the LMC in vitro. These findings may facilitate development of therapies for lysosomal storage disorders. PubMed: 33980489DOI: 10.1126/sciadv.abf4155 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.59 Å) |
Structure validation
Download full validation report
