The Est3 protein associates with yeast telomerase through an OB-fold domain.
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.
Lee
Jaesung
J
The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolia, California 92037, USA.
Mandell
Edward K
EK
Tucey
Timothy M
TM
Morris
Danna K
DK
Lundblad
Victoria
V
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005658:Fungi / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000089804:Shelterin Complex; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
C495876:ACD protein, human; D005656:Fungal Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase