Structure of the RNA-binding domain of telomerase: implications for RNA recognition and binding.
Telomerase, a ribonucleoprotein complex, replicates the linear ends of eukaryotic chromosomes, thus taking care of the "end of replication problem." TERT contains an essential and universally conserved domain (TRBD) that makes extensive contacts with the RNA (TER) component of the holoenzyme, and this interaction is thought to facilitate TERT/TER assembly and repeat-addition processivity. Here, we present a high-resolution structure of TRBD from Tetrahymena thermophila. The nearly all-helical structure comprises a nucleic acid-binding fold suitable for TER binding. An extended pocket on the surface of the protein, formed by two conserved motifs (CP and T motifs) comprises TRBD's RNA-binding pocket. The width and the chemical nature of this pocket suggest that it binds both single- and double-stranded RNA, possibly stem I, and the template boundary element (TBE). Moreover, the structure provides clues into the role of this domain in TERT/TER stabilization and telomerase repeat-addition processivity.
Rouda
Susan
S
Gene Expression and Regulation Program, The Wistar Institute, University of Pennsylvania, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Skordalakes
Emmanuel
E
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D016415:Sequence Alignment; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016808:Tetrahymena thermophila / Q000201:enzymology / Q000378:metabolism
D012313:RNA; D019098:Telomerase