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.

中文翻译：

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在白色念珠菌端粒酶蛋白 Est3 中提出的具有蛋白质相互作用表面的 OB 折叠。

更短的端粒 3 (Est3) 是一种重要的端粒酶调节亚基，被认为是萌芽酵母所独有的。在这里，我们使用多序列比对和隐藏马尔可夫模型-隐藏马尔可夫模型 (HMM-HMM) 比较来揭示 Est3 和哺乳动物端粒蛋白 Tpp1 之间的潜在相似性。对白色念珠菌 Est3 的位点特异性突变体的分析揭示了在 Est3 和 Tpp1 之间保守的残基与 Est3 特有的残基之间的功能区别。虽然这两种残基对体内端粒维持很重要，但只有前者有助于体外端粒酶活性并促进 Est3 与端粒酶核心成分的结合。与蛋白质-蛋白质相互作用中的功能一致，Est3 和 Tpp1 共有的残基映射到 OB 折叠模型结构的一个面，远离标准核酸结合表面。我们建议 Est3 和 Tpp1 的 OB 折叠结构域介导端粒酶调节中的保守功能。