Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions.
Publication Type:Journal Article
Source:Science, Volume 350, Issue 6260, p.aab4070 (2015)
Keywords:Catalytic Domain, Cryoelectron Microscopy, Crystallography, X-Ray, DNA, Single-Stranded, Holoenzymes, Protein Binding, Protein Conformation, Protein Subunits, Replication Protein A, RNA, Telomerase, Telomere, Telomere Homeostasis, Telomere-Binding Proteins, Tetrahymena
<p>Telomerase helps maintain telomeres by processive synthesis of telomere repeat DNA at their 3'-ends, using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). We report the cryo-electron microscopy structure of Tetrahymena telomerase at ~9 angstrom resolution. In addition to seven known holoenzyme proteins, we identify two additional proteins that form a complex (TEB) with single-stranded telomere DNA-binding protein Teb1, paralogous to heterotrimeric replication protein A (RPA). The p75-p45-p19 subcomplex is identified as another RPA-related complex, CST (CTC1-STN1-TEN1). This study reveals the paths of TER in the TERT-TER-p65 catalytic core and single-stranded DNA exit; extensive subunit interactions of the TERT essential N-terminal domain, p50, and TEB; and other subunit identities and structures, including p19 and p45C crystal structures. Our findings provide structural and mechanistic insights into telomerase holoenzyme function. </p>