title: Conservation and dispersion of sequence and function in fungal TRK potassium transporters: focus on Candida albicans.
abstract: TRK proteins - essential potassium (K(+)) transporters in fungi and bacteria, as well as in plants - are generally absent from animal cells, which makes them potential targets for selective drug action. Indeed, in the human pathogen Candida albicans, the single TRK isoform (CaTrk1p) has recently been demonstrated to be required for activity of histidine-rich salivary antimicrobial peptides (histatins). Background for a detailed molecular investigation of TRK-protein design and function is provided here in sequence analysis and quantitative functional comparison of CaTrk1p with its better-known homologues from Saccharomyces cerevisiae. Among C. albicans strains (ATCC 10261, SC5314, WO-1), the DNA sequence is essentially devoid of single nucleotide polymorphisms in regions coding for evolutionarily conserved segments of the protein, meaning the four intramembranal [membrane-pore-membrane (MPM)] segments thought to be involved directly with the conduction of K(+) ions. Among 48 fungal (ascomycete) TRK homologues now described by complete sequences, clades (but not the detailed order within clades) appear conserved for all four MPM segments, independently assessed. The primary function of TRK proteins, 'active' transport of K(+) ions, is quantitatively conserved between C. albicans and S. cerevisiae. However, the secondary function, chloride efflux channeling, is present but poorly conserved between the two species, being highly variant with respect to activation velocity, amplitude, flickering (channel-like) behavior, pH dependence, and inhibitor sensitivity.
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Miranda
authors.forename: Esther
authors.initials: E
authors.lastname: Bashi
authors.forename: Slavena
authors.initials: S
authors.lastname: Vylkova
authors.forename: Mira
authors.initials: M
authors.lastname: Edgerton
authors.forename: Clifford
authors.initials: C
authors.lastname: Slayman
authors.forename: Alberto
authors.initials: A
authors.lastname: Rivetta
mesh_terms: D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D017124:Conserved Sequence; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011188:Potassium / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D027682:Cation Transport Proteins; D002712:Chlorides; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011188:Potassium