title: The Candida albicans Sup35p protein (CaSup35p): function, prion-like behaviour and an associated polyglutamine length polymorphism.
abstract: The Sup35p protein of Saccharomyces cerevisiae is an essential translation factor whose prion-like properties give rise to the non-Mendelian genetic element [PSI(+)]. In this study the SUP35 gene from the related yeast species Candida albicans has been characterized. The CaSUP35 gene encodes a protein (CaSup35p) of 729 aa which shows 65% amino acid identity to the S. cerevisiae Sup35p protein (ScSup35p), with the C-terminal region showing greater identity (79%) than the N-terminal region. The full-length CaSup35p can functionally replace ScSup35p in S. cerevisiae although complementation is only complete when CaSup35p is overexpressed. Complementation only requires expression of the CaSup35p C domain. In S. cerevisiae the full-length CaSup35p is unable to establish a prion-like aggregated state even in the presence of endogenous ScSup35p prion 'seeds', thus confirming the existence of a species barrier in fungal prion propagation. Subcellular localization studies in C. albicans show that although CaSup35p is normally ribosome-associated, when not ribosome-associated, it does not form pelletable high-molecular-mass aggregates characteristic of the ScSup35p in [PSI(+)] strains. Unlike the ScSup35p, the CaSup35p N domain contains a number of polyglutamine repeats although it does contain seven copies of the peptide GGYQQ that is repeated in the ScSup35p N domain. Analysis of the CaSUP35 gene from 14 different strains of C. albicans identified four naturally occurring polymorphisms associated with changes in the length of the largest of the polyglutamine repeats. These findings have important implications for the evolution of fungal prion genes.
authors.affiliation: Centro de Genética e Biologia Molecular, Universidade de Lisboa, Portugal2.|Research School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK1.
authors.forename: Catarina
authors.initials: C
authors.lastname: Resende
authors.affiliation: Research School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK1.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Parham
authors.affiliation: Research School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK1.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tinsley
authors.affiliation: Centro de Genética e Biologia Molecular, Universidade de Lisboa, Portugal2.|Research School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK1.
authors.forename: Paulo
authors.initials: P
authors.lastname: Ferreira
authors.affiliation: Centro de Genética e Biologia Molecular, Universidade de Lisboa, Portugal2.
authors.forename: Júlio A B
authors.initials: JAB
authors.lastname: Duarte
authors.affiliation: Research School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK1.
authors.forename: Mick F
authors.initials: MF
authors.lastname: Tuite
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development; D017931:DNA Primers; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D005838:Genotype; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors; D010455:Peptides / Q000235:genetics*; D010957:Plasmids; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011328:Prions / Q000737:chemistry / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D005656:Fungal Proteins; D010454:Peptide Termination Factors; D010455:Peptides; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C459790:Sup35 protein, Candida albicans; C097188:polyglutamine