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

Nature Structural & Molecular Biology volume 15, pages 990–997 (2008)Cite this article

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.

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Figure 1: Est3 is an OB-fold–containing protein with structural similarity to the OB-fold of TPP1.
Figure 2: Residues that are conserved between Est3 and Tpp1 are located in the core of the OB-fold.
Figure 3: Detailed phenotypic analysis of mutations in predicted surface residues of Est3.
Figure 4: An interaction surface on one face of the OB-fold mediates association of Est3 with the telomerase enzyme.

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Acknowledgements

We thank L. Ricks and E. Ford for outstanding technical assistance. This research was supported by grant AG11728 from the US National Institutes of Health.

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Author notes

  1. Jaesung Lee and Edward K Mandell: These authors contributed equally to this work.

Authors and Affiliations

  1. The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA

    Jaesung Lee, Edward K Mandell, Timothy M Tucey & Victoria Lundblad

  2. Graduate Program in Cell and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, USA

    Edward K Mandell & Danna K Morris

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  1. Jaesung Lee
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Correspondence to Victoria Lundblad.

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Lee, J., Mandell, E., Tucey, T. et al. The Est3 protein associates with yeast telomerase through an OB-fold domain. Nat Struct Mol Biol 15, 990–997 (2008). https://doi.org/10.1038/nsmb.1472

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