The Est3 protein associates with yeast telomerase through an OB-fold domain

Nat Struct Mol Biol. 2008 Sep;15(9):990-7. doi: 10.1038/nsmb.1472.

Abstract

The Ever shorter telomeres 3 (Est3) protein is a small regulatory subunit of yeast telomerase which is dispensable for enzyme catalysis but essential for telomere replication in vivo. Using structure prediction combined with in vivo characterization, we show here that Est3 consists of a predicted OB (oligosaccharide/oligonucleotide binding)-fold. We used mutagenesis of predicted surface residues to generate a functional map of one surface of Est3, identifying a site that mediates association with the telomerase complex. Unexpectedly, the predicted OB-fold of Est3 is structurally similar to the OB-fold of the human TPP1 protein, despite the fact that Est3 and TPP1, as components of telomerase and a telomere-capping complex, respectively, perform functionally distinct tasks at chromosome ends. Our analysis of Est3 may be instructive in generating comparable missense mutations on the surface of the OB-fold domain of TPP1.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Fungi / genetics
  • Fungi / metabolism
  • Genes, Fungal
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Telomerase / chemistry*
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere-Binding Proteins / chemistry
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Fungal Proteins
  • PTOP protein, human
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • Telomerase