title: A structural model for facultative anion channels in an oligomeric membrane protein: the yeast TRK (K(+)) system.
abstract: TRK transporters, a class of proteins which generally carry out the bulk of K(+) accumulation in plants, fungi, and bacteria, mediate ion currents driven by the large membrane voltages (-150 to -250 mV) common to non-animal cells. Bacterial TRK proteins resemble K(+) channels in their primary sequence, crystallize as membrane dimers having intramolecular K(+)-channel-like folding, and complex with a cytoplasmic collar formed of four RCK domains (Nature 471:336, 2011; Ibid 496:324, 2013). Fungal TRK proteins appear simpler in form than the bacterial members, but do possess two special features: a large built-in regulatory domain, and a highly conserved pair of transmembrane helices (TM7 and TM8, ahead of the C-terminus), which were postulated to facilitate intramembranal oligomerization (Biophys. J. 77:789, 1999; FEMS Yeast Res. 9:278, 2009). A surprising associated functional process in the fungal proteins which have been explored (Saccharomyces, Candida, and Neurospora) is facilitation of channel-like chloride efflux. That process is suppressed by osmoprotective agents, appears to involve hydrophobic gating, and strongly resembles conduction by Cys-loop ligand-gated anion channels. And it leads to a rather general hypothesis: that the thermodynamic tendency for hydrophobic or amphipathic transmembrane helices to self-organize into oligomers can create novel ionic pathways through biological membranes: fundamental hydrophobic nanopores, pathways of low selectivity governed by the chaotropic behavior of individual ionic species and under the strong influence of membrane voltage.
authors.affiliation: Departamento de Bioquimica, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Coyoacan, 04510, Mexico, D.F., Mexico. pardov@laguna.fmedic.unam.mx.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Pardo
authors.affiliation: Departamento de Bioquimica, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Coyoacan, 04510, Mexico, D.F., Mexico. martin@bq.unam.mx.
authors.forename: Martin
authors.initials: M
authors.lastname: González-Andrade
authors.affiliation: Department of Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA. kenneth.allen@yale.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Allen
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan. tkuroda@cc.okayama-u.ac.jp.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA. clifford.slayman@yale.edu.
authors.forename: Clifford L
authors.identifier: http://orcid.org/0000-0002-3029-2054
authors.initials: CL
authors.lastname: Slayman
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA. alberto.rivetta@yale.edu.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rivetta
mesh_terms: D000595:Amino Acid Sequence; D002712:Chlorides / Q000378:metabolism*; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D002712:Chlorides; D015221:Potassium Channels; D029701:Saccharomyces cerevisiae Proteins; D011188:Potassium
keywords: Chaotropic anions; Compatible solutes; Ligand-gated channels; Microbial chloride efflux; TRK-potassium transporters