title: A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3.
abstract: Ever shorter telomeres 3 (Est3) is an essential telomerase regulatory subunit thought to be unique to budding yeasts. Here we use multiple sequence alignment and hidden Markov model-hidden Markov model (HMM-HMM) comparison to uncover potential similarities between Est3 and the mammalian telomeric protein Tpp1. Analysis of site-specific mutants of Candida albicans Est3 revealed functional distinctions between residues that are conserved between Est3 and Tpp1 and those that are unique to Est3. Although both types of residues are important for telomere maintenance in vivo, only the former contributes to telomerase activity in vitro and facilitates the association of Est3 with telomerase core components. Consistent with a function in protein-protein interaction, the residues common to Est3 and Tpp1 map to one face of an OB-fold model structure, away from the canonical nucleic acid binding surface. We propose that Est3 and the OB-fold domain of Tpp1 mediate a conserved function in telomerase regulation.
authors.affiliation: Department of Microbiology & Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Yu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Neal F
authors.initials: NF
authors.lastname: Lue
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D005800:Genes, Fungal; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D000089804:Shelterin Complex; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: C495876:ACD protein, human; D004271:DNA, Fungal; D005656:Fungal Proteins; D011994:Recombinant Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase