Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1

Nat Commun. 2018 Mar 22;9(1):1192. doi: 10.1038/s41467-018-03606-0.


PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of π-π interactions, suggesting a potential PKD2L1 gating mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / chemistry*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Calcium Channels / ultrastructure
  • Cryoelectron Microscopy
  • Humans
  • Mice
  • Protein Conformation, alpha-Helical
  • Protein Domains
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / ultrastructure
  • TRPP Cation Channels / chemistry
  • TRPP Cation Channels / genetics
  • TRPP Cation Channels / metabolism


  • Calcium Channels
  • PKD2L1 protein, human
  • Pkd2l1 protein, mouse
  • Receptors, Cell Surface
  • TRPP Cation Channels
  • polycystic kidney disease 2 protein