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Crystal structures of N-terminally truncated telomerase reverse transcriptase from fungi‡.
Nucleic Acids Res, 49(8):4768-4781.
Telomerase plays critical roles in cellular aging, in the emergence and/ordevelopment of cancer, and in the capacity for stem-cell renewal, consists of acatalytic telomerase reverse transcriptase (TERT) and a template-encoding RNA(TER). TERs from diverse organisms contain two conserved structural elements: thetemplate-pseudoknot (T-PK) and a helical three-way junction (TWJ).Species-specific features of the structure and function of telomerase makeobtaining a more in-depth understanding of the molecular mechanism of telomeraseparticularly important. Here, we report the first structural studies ofN-terminally truncated TERTs from Candida albicans and Candida tropicalis in apoform and complexed with their respective TWJs in several conformations. We foundthat Candida TERT proteins perform only one round of telomere addition in thepresence or absence of PK/TWJ and display standard reverse transcriptaseactivity. The C-terminal domain adopts at least two extreme conformations andundergoes conformational interconversion, which regulates the catalytic activity.Most importantly, we identified a conserved tertiary structural motif, called theU-motif, which interacts with the reverse transcriptase domain and is crucial forcatalytic activity. Together these results shed new light on the structure andmechanics of fungal TERTs, which show common TERT characteristics, but alsodisplay species-specific features.
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