5T4D

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

Summary for 5T4D

• Entry DOI: 10.2210/pdb5t4d/pdb
• EMDB information: 8354 8355 8356
• Descriptor: hPKD:198-703, Polycystin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: trp channel, pkd2, nanodisc, trpp, metal transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 240371.08

Authors

Shen, P.S.,Yang, X.,DeCaen, P.G.,Liu, X.,Bulkley, D.,Clapham, D.E.,Cao, E. (deposition date: 2016-08-29, release date: 2016-11-02, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3 Å)