Crystal structures of N-terminally truncated telomerase reverse transcriptase from fungi

Autor: Ze-Yu Song, Daniel Auguin, Bo Sun, Wei-Fei Chen, Xu-Guang Xi, Shuo-Xing Dou, Liu-Tao Zhai, Stéphane Réty
Přispěvatelé: Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Ecole des Hautes Etudes Commerciales (HEC Paris), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), Université d'Orléans (UO)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ShanghaiTech University [Shanghai], Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), University of Chinese Academy of Sciences [Beijing] (UCAS), Northwest A and F University, xi, Xu-Guang, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nucleic Acids Research
Nucleic Acids Research, Oxford University Press, 2021, 49 (8), pp.4768-4781. ⟨10.1093/nar/gkab261⟩
Nucleic Acids Research, 2021, 49 (8), pp.4768-4781. ⟨10.1093/nar/gkab261⟩
ISSN: 0305-1048
1362-4962
Popis: Telomerase plays critical roles in cellular aging, in the emergence and/or development of cancer, and in the capacity for stem-cell renewal, consists of a catalytic telomerase reverse transcriptase (TERT) and a template-encoding RNA (TER). TERs from diverse organisms contain two conserved structural elements: the template-pseudoknot (T-PK) and a helical three-way junction (TWJ). Species-specific features of the structure and function of telomerase make obtaining a more in-depth understanding of the molecular mechanism of telomerase particularly important. Here, we report the first structural studies of N-terminally truncated TERTs from Candida albicans and Candida tropicalis in apo form and complexed with their respective TWJs in several conformations. We found that Candida TERT proteins perform only one round of telomere addition in the presence or absence of PK/TWJ and display standard reverse transcriptase activity. The C-terminal domain adopts at least two extreme conformations and undergoes conformational interconversion, which regulates the catalytic activity. Most importantly, we identified a conserved tertiary structural motif, called the U-motif, which interacts with the reverse transcriptase domain and is crucial for catalytic activity. Together these results shed new light on the structure and mechanics of fungal TERTs, which show common TERT characteristics, but also display species-specific features.
Databáze: OpenAIRE
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