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A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3

Nature Structural & Molecular Biology volume 15, pages 985–989 (2008)Cite this article

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.

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Figure 1: Sequence and structural similarity between Est3 and Tpp1 homologs.
Figure 2: The effects of C. albicans Est3 mutations on telomere maintenance and telomerase association.
Figure 3: The effects of C. albicans Est3 mutations on telomerase primer extension activity in vitro.

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Acknowledgements

We thank A. Den and J. Kang for technical assistance. This work was supported by grants from the US National Institutes of Health (GM069507 to N.F.L. and GM083015 to M.L.).

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Authors and Affiliations

  1. Department of Microbiology & Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, 10065, New York, USA

    Eun Young Yu & Neal F Lue

  2. Department of Biological Chemistry, University of Michigan Medical School, 5301D MSRB III, 1150 West Medical Center Drive, Ann Arbor, 48109, Michigan, USA

    Feng Wang & Ming Lei

Authors
  1. Eun Young Yu
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  2. Feng Wang
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  4. Neal F Lue
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Contributions

E.Y.Y. performed the experiments and analyzed the data. F.W. and M.L. contributed reagents and helped interpret the data. N.F.L. conceived the project, analyzed the experiments and wrote the paper.

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Correspondence to Neal F Lue.

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The authors declare no competing financial interests.

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Young Yu, E., Wang, F., Lei, M. et al. A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3. Nat Struct Mol Biol 15, 985–989 (2008). https://doi.org/10.1038/nsmb.1471

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