5K47

CryoEM structure of the human Polycystin-2/PKD2 TRP channel

5K47 の概要

• エントリーDOI: 10.2210/pdb5k47/pdb
• EMDBエントリー: 8200
• 分子名称: 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)
• 機能のキーワード: ion channel, transient receptor potential channel, polycystic kidney disease, structural genomics, structural genomics consortium, sgc, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 259413.94

構造登録者

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) (登録日: 2016-05-20, 公開日: 2016-08-24, 最終更新日: 2024-10-23)

主引用文献

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

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: 27991905
DOI: 10.1038/nsmb.3343

実験手法

ELECTRON MICROSCOPY (4.22 Å)