6R4L
Crystal structure of S. cerevisia Niemann-Pick type C protein NCR1
Summary for 6R4L
| Entry DOI | 10.2210/pdb6r4l/pdb |
| Descriptor | NPC intracellular cholesterol transporter 1-related protein 1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ERGOSTEROL, ... (4 entities in total) |
| Functional Keywords | vacuole, ergosterol, lipid transport, membrane protein |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
| Total number of polymer chains | 1 |
| Total formula weight | 137503.99 |
| Authors | Winkler, M.B.L.,Kidmose, R.T.,Pedersen, B.P. (deposition date: 2019-03-22, release date: 2019-09-25, Last modification date: 2024-01-24) |
| Primary citation | Winkler, M.B.L.,Kidmose, R.T.,Szomek, M.,Thaysen, K.,Rawson, S.,Muench, S.P.,Wustner, D.,Pedersen, B.P. Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins. Cell, 179:485-497.e18, 2019 Cited by PubMed Abstract: Niemann-Pick type C (NPC) proteins are essential for sterol homeostasis, believed to drive sterol integration into the lysosomal membrane before redistribution to other cellular membranes. Here, using a combination of crystallography, cryo-electron microscopy, and biochemical and in vivo studies on the Saccharomyces cerevisiae NPC system (NCR1 and NPC2), we present a framework for sterol membrane integration. Sterols are transferred between hydrophobic pockets of vacuolar NPC2 and membrane-protein NCR1. NCR1 has its N-terminal domain (NTD) positioned to deliver a sterol to a tunnel connecting NTD to the luminal membrane leaflet 50 Å away. A sterol is caught inside this tunnel during transport, and a proton-relay network of charged residues in the transmembrane region is linked to this tunnel supporting a proton-driven transport mechanism. We propose a model for sterol integration that clarifies the role of NPC proteins in this essential eukaryotic pathway and that rationalizes mutations in patients with Niemann-Pick disease type C. PubMed: 31543266DOI: 10.1016/j.cell.2019.08.038 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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