Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex

Nat Commun. 2012;3:1252. doi: 10.1038/ncomms2257.

Abstract

Polycystic kidney disease (PKD) family proteins associate with transient receptor potential (TRP) channel family proteins to form functionally important complexes. PKD proteins differ from known ion channel-forming proteins and are generally thought to act as membrane receptors. Here we find that PKD1L3, a PKD protein, functions as a channel-forming subunit in an acid-sensing heteromeric complex formed by PKD1L3 and TRPP3, a TRP channel protein. Single amino-acid mutations in the putative pore region of both proteins alter the channel's ion selectivity. The PKD1L3/TRPP3 complex in the plasma membrane of live cells contains one PKD1L3 and three TRPP3. A TRPP3 C-terminal coiled-coil domain forms a trimer in solution and in crystal, and has a crucial role in the assembly and surface expression of the PKD1L3/TRPP3 complex. These results demonstrate that PKD subunits constitute a new class of channel-forming proteins, enriching our understanding of the function of PKD proteins and PKD/TRPP complexes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution / genetics
  • Amino Acid Substitution / physiology
  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / physiology
  • Cell Membrane Permeability / physiology
  • Dimethylamines / metabolism
  • Humans
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / physiology*
  • Macromolecular Substances / metabolism
  • Magnesium / metabolism
  • Methylamines / metabolism
  • Mice
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology
  • Sequence Alignment
  • Xenopus

Substances

  • Calcium Channels
  • Dimethylamines
  • Ion Channels
  • Macromolecular Substances
  • Methylamines
  • PKD1L3 protein, human
  • PKD2L1 protein, human
  • Receptors, Cell Surface
  • dimethylamine
  • Magnesium
  • trimethylamine

Associated data

  • PDB/4GIF