5K47
CryoEM structure of the human Polycystin-2/PKD2 TRP channel
Summary for 5K47
| Entry DOI | 10.2210/pdb5k47/pdb |
| EMDB information | 8200 |
| 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 (3 entities in total) |
| Functional Keywords | ion channel, transient receptor potential channel, polycystic kidney disease, structural genomics, structural genomics consortium, sgc, transport protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 259413.94 |
| Authors | Pike, A.C.W.,Grieben, M.,Shintre, C.A.,Tessitore, A.,Shrestha, L.,Mukhopadhyay, S.,Mahajan, P.,Chalk, R.,Burgess-Brown, N.A.,Huiskonen, J.T.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Carpenter, E.P.,Structural Genomics Consortium (SGC) (deposition date: 2016-05-20, release date: 2016-08-24, Last modification date: 2024-10-23) |
| Primary citation | Grieben, M.,Pike, A.C.,Shintre, C.A.,Venturi, E.,El-Ajouz, S.,Tessitore, A.,Shrestha, L.,Mukhopadhyay, S.,Mahajan, P.,Chalk, R.,Burgess-Brown, N.A.,Sitsapesan, R.,Huiskonen, J.T.,Carpenter, E.P. Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2). Nat. Struct. Mol. Biol., 24:114-122, 2017 Cited by PubMed Abstract: Mutations in either polycystin-1 (PC1 or PKD1) or polycystin-2 (PC2, PKD2 or TRPP1) cause autosomal-dominant polycystic kidney disease (ADPKD) through unknown mechanisms. Here we present the structure of human PC2 in a closed conformation, solved by electron cryomicroscopy at 4.2-Å resolution. The structure reveals a novel polycystin-specific 'tetragonal opening for polycystins' (TOP) domain tightly bound to the top of a classic transient receptor potential (TRP) channel structure. The TOP domain is formed from two extensions to the voltage-sensor-like domain (VSLD); it covers the channel's endoplasmic reticulum lumen or extracellular surface and encloses an upper vestibule, above the pore filter, without blocking the ion-conduction pathway. The TOP-domain fold is conserved among the polycystins, including the homologous channel-like region of PC1, and is the site of a cluster of ADPKD-associated missense variants. Extensive contacts among the TOP-domain subunits, the pore and the VSLD provide ample scope for regulation through physical and chemical stimuli. PubMed: 27991905DOI: 10.1038/nsmb.3343 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.22 Å) |
Structure validation
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