Crystal structures of N-terminally truncated telomerase reverse transcriptase from fungi‡.
Amino Acid Motifs
/ genetics
Candida albicans
/ chemistry
Candida tropicalis
/ chemistry
Catalysis
Catalytic Domain
/ genetics
Chromatography, Gel
Crystallography, X-Ray
Dynamic Light Scattering
Escherichia coli
/ metabolism
In Vitro Techniques
Models, Molecular
Mutation
Recombinant Proteins
Telomerase
/ chemistry
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
07 05 2021
07 05 2021
Historique:
accepted:
05
04
2021
revised:
28
03
2021
received:
20
10
2020
pubmed:
16
4
2021
medline:
17
6
2021
entrez:
15
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33856462
pii: 6226674
doi: 10.1093/nar/gkab261
pmc: PMC8096264
doi:
Substances chimiques
Recombinant Proteins
0
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4768-4781Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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