5T4D

Cryo-EM structure of Polycystic Kidney Disease protein 2 (PKD2), residues 198-703

5T4D の概要

• エントリーDOI: 10.2210/pdb5t4d/pdb
• EMDBエントリー: 8354 8355 8356
• 分子名称: hPKD:198-703, Polycystin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: trp channel, pkd2, nanodisc, trpp, metal transport
• 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: 240371.08

構造登録者

Shen, P.S.,Yang, X.,DeCaen, P.G.,Liu, X.,Bulkley, D.,Clapham, D.E.,Cao, E. (登録日: 2016-08-29, 公開日: 2016-11-02, 最終更新日: 2024-11-13)

主引用文献

Shen, P.S.,Yang, X.,DeCaen, P.G.,Liu, X.,Bulkley, D.,Clapham, D.E.,Cao, E.
The Structure of the Polycystic Kidney Disease Channel PKD2 in Lipid Nanodiscs.
Cell, 167:763-773.e11, 2016

PubMed Abstract: The Polycystic Kidney Disease 2 (Pkd2) gene is mutated in autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic disorders. Here, we present the cryo-EM structure of PKD2 in lipid bilayers at 3.0 Å resolution, which establishes PKD2 as a homotetrameric ion channel and provides insight into potential mechanisms for its activation. The PKD2 voltage-sensor domain retains two of four gating charges commonly found in those of voltage-gated ion channels. The PKD2 ion permeation pathway is constricted at the selectivity filter and near the cytoplasmic end of S6, suggesting that two gates regulate ion conduction. The extracellular domain of PKD2, a hotspot for ADPKD pathogenic mutations, contributes to channel assembly and strategically interacts with the transmembrane core, likely serving as a physical substrate for extracellular stimuli to allosterically gate the channel. Finally, our structure establishes the molecular basis for the majority of pathogenic mutations in Pkd2-related ADPKD.

PubMed: 27768895
DOI: 10.1016/j.cell.2016.09.048

実験手法

ELECTRON MICROSCOPY (3 Å)