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Crystal structure of the essential
N-terminal domain of telomerase reverse transcriptase
Steven A
Jacobs, Elaine R Podell & Thomas R Cech
Howard Hughes Medical Institute,
Department of Chemistry and Biochemistry, University of Colorado,
Boulder, Colorado 80309-0215, USA.
Correspondence should be addressed to Thomas R Cech president@hhmi.org
Telomerase,
a ribonucleoprotein enzyme, adds telomeric DNA repeats to the ends of
linear chromosomes.
Here
we report the first high-resolution structure of any portion of the
telomerase reverse transcriptase, the telomerase essential N-terminal
(TEN) domain from Tetrahymena thermophila.
The
structure, which seems to represent a novel protein fold, shows
phylogenetically conserved amino acid residues in a groove on its
surface.
These
residues are crucial for telomerase catalytic activity, and several of
them are required for sequence-specific binding of a single-stranded
telomeric DNA primer.
The
positively charged C terminus, which becomes ordered upon interaction
with other macromolecules, is involved in binding RNA in a
non–sequence-specific manner.
The
TEN domain's ability to bind both RNA and telomeric DNA, coupled with
the notably strong effects on activity upon mutagenesis of single
surface residues, suggest how this domain contributes to telomerase
catalysis.
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