5UPH
Lipids bound lysosomal integral membrane protein 2
Summary for 5UPH
| Entry DOI | 10.2210/pdb5uph/pdb |
| 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, ... (7 entities in total) |
| Functional Keywords | lysosomal integral membrane protein 2; phospholipid receptor, membrane protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 103834.70 |
| Authors | Conrad, K.S.,Liu, S. (deposition date: 2017-02-03, release date: 2017-12-13, Last modification date: 2024-11-06) |
| Primary citation | Conrad, K.S.,Cheng, T.W.,Ysselstein, D.,Heybrock, S.,Hoth, L.R.,Chrunyk, B.A.,Am Ende, C.W.,Krainc, D.,Schwake, M.,Saftig, P.,Liu, S.,Qiu, X.,Ehlers, M.D. Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies. Nat Commun, 8:1908-1908, 2017 Cited by PubMed Abstract: Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) contributes to endosomal and lysosomal function. LIMP-2 deficiency is associated with neurological abnormalities and kidney failure and, as an acid glucocerebrosidase receptor, impacts Gaucher and Parkinson's diseases. Here we report a crystal structure of a LIMP-2 luminal domain dimer with bound cholesterol and phosphatidylcholine. Binding of these lipids alters LIMP-2 from functioning as a glucocerebrosidase-binding monomer toward a dimeric state that preferentially binds anionic phosphatidylserine over neutral phosphatidylcholine. In cellular uptake experiments, LIMP-2 facilitates transport of phospholipids into murine fibroblasts, with a strong substrate preference for phosphatidylserine. Taken together, these biophysical and cellular studies define the structural basis and functional importance of a form of LIMP-2 for lipid trafficking. We propose a model whereby switching between monomeric and dimeric forms allows LIMP-2 to engage distinct binding partners, a mechanism that may be shared by SR-BI and CD36, scavenger receptor proteins highly homologous to LIMP-2. PubMed: 29199275DOI: 10.1038/s41467-017-02044-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
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