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-Structure paper
タイトル | Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2). |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 24, Issue 2, Page 114-122, Year 2017 |
掲載日 | 2016年12月19日 |
著者 | Mariana Grieben / Ashley C W Pike / Chitra A Shintre / Elisa Venturi / Sam El-Ajouz / Annamaria Tessitore / Leela Shrestha / Shubhashish Mukhopadhyay / Pravin Mahajan / Rod Chalk / Nicola A Burgess-Brown / Rebecca Sitsapesan / Juha T Huiskonen / Elisabeth P Carpenter / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:27991905 |
手法 | EM (単粒子) |
解像度 | 4.22 Å |
構造データ | |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | TRANSPORT PROTEIN / ion channel / transient receptor potential channel / polycystic kidney disease / Structural Genomics / Structural Genomics Consortium / SGC |