8QEE
S. cerevisia Niemann-Pick type C protein NCR1 in Peptidisc at pH 7.5
Summary for 8QEE
| Entry DOI | 10.2210/pdb8qee/pdb |
| Related | 8QEB 8QEC 8QED |
| EMDB information | 18350 18351 18352 18353 |
| Descriptor | NPC intracellular sterol transporter 1-related protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CHOLESTEROL HEMISUCCINATE, ... (5 entities in total) |
| Functional Keywords | sterol transport, vacuole, lysosome, lipid transport, membrane protein |
| Biological source | Saccharomyces cerevisiae (baker's yeast) |
| Total number of polymer chains | 1 |
| Total formula weight | 134329.85 |
| Authors | Frain, K.M.,Dedic, E.,Nel, L.,Olesen, E.,Stokes, D.,Panyella Pedersen, B. (deposition date: 2023-08-31, release date: 2023-10-18, Last modification date: 2024-11-13) |
| Primary citation | Frain, K.M.,Dedic, E.,Nel, L.,Bohush, A.,Olesen, E.,Thaysen, K.,Wustner, D.,Stokes, D.L.,Pedersen, B.P. Conformational changes in the Niemann-Pick type C1 protein NCR1 drive sterol translocation. Proc.Natl.Acad.Sci.USA, 121:e2315575121-e2315575121, 2024 Cited by PubMed Abstract: The membrane protein Niemann-Pick type C1 (NPC1, named NCR1 in yeast) is central to sterol homeostasis in eukaryotes. NCR1 is localized to the vacuolar membrane, where it is suggested to carry sterols across the protective glycocalyx and deposit them into the vacuolar membrane. However, documentation of a vacuolar glycocalyx in fungi is lacking, and the mechanism for sterol translocation has remained unclear. Here, we provide evidence supporting the presence of a glycocalyx in isolated vacuoles and report four cryo-EM structures of NCR1 in two distinct conformations, named tense and relaxed. These two conformations illustrate the movement of sterols through a tunnel formed by the luminal domains, thus bypassing the barrier presented by the glycocalyx. Based on these structures and on comparison with other members of the Resistance-Nodulation-Division (RND) superfamily, we propose a transport model that links changes in the luminal domains with a cycle of protonation and deprotonation within the transmembrane region of the protein. Our model suggests that NPC proteins work by a generalized RND mechanism where the proton motive force drives conformational changes in the transmembrane domains that are allosterically coupled to luminal/extracellular domains to promote sterol transport. PubMed: 38568972DOI: 10.1073/pnas.2315575121 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.43 Å) |
Structure validation
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