5MKF
cryoEM Structure of Polycystin-2 in complex with calcium and lipids
Summary for 5MKF
| Entry DOI | 10.2210/pdb5mkf/pdb |
| EMDB information | 3524 |
| Descriptor | Polycystin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | ca2+ signaling, cryoem, membrane protein structure, polycystin-2, trp channel, transport protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 451223.77 |
| Authors | Wilkes, M.,Madej, M.G.,Ziegler, C. (deposition date: 2016-12-04, release date: 2017-01-18, Last modification date: 2020-07-29) |
| Primary citation | Wilkes, M.,Madej, M.G.,Kreuter, L.,Rhinow, D.,Heinz, V.,De Sanctis, S.,Ruppel, S.,Richter, R.M.,Joos, F.,Grieben, M.,Pike, A.C.,Huiskonen, J.T.,Carpenter, E.P.,Kuhlbrandt, W.,Witzgall, R.,Ziegler, C. Molecular insights into lipid-assisted Ca(2+) regulation of the TRP channel Polycystin-2. Nat. Struct. Mol. Biol., 24:123-130, 2017 Cited by PubMed Abstract: Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca signaling pathways. Malfunctioning Ca regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here we report two cryo-EM structures of distinct channel states of full-length human PC2 in complex with lipids and cations. The structures reveal conformational differences in the selectivity filter and in the large exoplasmic domain (TOP domain), which displays differing N-glycosylation. The more open structure has one cation bound below the selectivity filter (single-ion mode, PC2), whereas multiple cations are bound along the translocation pathway in the second structure (multi-ion mode, PC2). Ca binding at the entrance of the selectivity filter suggests Ca blockage in PC2, and we observed density for the Ca-sensing C-terminal EF hand in the unblocked PC2 state. The states show altered interactions of lipids with the pore loop and TOP domain, thus reflecting the functional diversity of PC2 at different locations, owing to different membrane compositions. PubMed: 28092368DOI: 10.1038/nsmb.3357 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.2 Å) |
Structure validation
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