title: Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex.
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.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Maximilian H
authors.initials: MH
authors.lastname: Ulbrich
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Li
authors.forename: Scott
authors.initials: S
authors.lastname: Dobbins
authors.forename: Wei K
authors.initials: WK
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
authors.forename: Ehud Y
authors.initials: EY
authors.lastname: Isacoff
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D004123:Dimethylamines / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D046911:Macromolecular Substances / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008744:Methylamines / Q000378:metabolism; D051379:Mice; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D014981:Xenopus
chemical_list: D015220:Calcium Channels; D004123:Dimethylamines; D007473:Ion Channels; D046911:Macromolecular Substances; D008744:Methylamines; C550142:PKD1L3 protein, human; C117185:PKD2L1 protein, human; D011956:Receptors, Cell Surface; C034516:dimethylamine; D008274:Magnesium; C023336:trimethylamine