title: Crystal structure of the essential N-terminal domain of telomerase reverse transcriptase.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Jacobs
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Podell
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003460:Crystallization; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D016415:Sequence Alignment; D019098:Telomerase / Q000737:chemistry*; D016615:Telomere / Q000235:genetics; D016808:Tetrahymena thermophila / Q000201:enzymology*
chemical_list: D000596:Amino Acids; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D004247:DNA; D019098:Telomerase