4Q4B
Crystal structure of LIMP-2 (space group C2221)
Summary for 4Q4B
| Entry DOI | 10.2210/pdb4q4b/pdb |
| Related | 4Q4F |
| Descriptor | Lysosome membrane protein 2, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total) |
| Functional Keywords | lysosomal targeting, beta-glucocerebrosidase, ci-mpr, er, endosome, lysosome, cell adhesion |
| Biological source | Homo sapiens (human) |
| Cellular location | Lysosome membrane; Multi-pass membrane protein: Q14108 |
| Total number of polymer chains | 1 |
| Total formula weight | 53194.66 |
| Authors | Zhao, Y.,Ren, J.,Padilla-Parra, S.,Fry, L.E.,Stuart, D.I. (deposition date: 2014-04-14, release date: 2014-07-30, Last modification date: 2024-11-06) |
| Primary citation | Zhao, Y.,Ren, J.,Padilla-Parra, S.,Fry, E.E.,Stuart, D.I. Lysosome sorting of beta-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor. Nat Commun, 5:4321-4321, 2014 Cited by PubMed Abstract: The integral membrane protein LIMP-2 has been a paradigm for mannose 6-phosphate receptor (MPR) independent lysosomal targeting, binding to β-glucocerebrosidase (β-GCase) and directing it to the lysosome, before dissociating in the late-endosomal/lysosomal compartments. Here we report structural results illuminating how LIMP-2 binds and releases β-GCase according to changes in pH, via a histidine trigger, and suggesting that LIMP-2 localizes the ceramide portion of the substrate adjacent to the β-GCase catalytic site. Remarkably, we find that LIMP-2 bears P-Man9GlcNAc2 covalently attached to residue N325, and that it binds MPR, via mannose 6-phosphate, with a similar affinity to that observed between LIMP-2 and β-GCase. The binding sites for β-GCase and the MPR are functionally separate, so that a stable ternary complex can be formed. By fluorescence lifetime imaging microscopy, we also demonstrate that LIMP-2 interacts with MPR in living cells. These results revise the accepted view of LIMP-2-β-GCase lysosomal targeting. PubMed: 25027712DOI: 10.1038/ncomms5321 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.82 Å) |
Structure validation
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