Faculty Collaboration Database

A structurally conserved human and Tetrahymena telomerase catalytic core. Proc Natl Acad Sci U S A 2020 Dec 08;117(49):31078-31087

Date

11/25/2020

Pubmed ID

33229538

Pubmed Central ID

PMC7733840

DOI

10.1073/pnas.2011684117

Scopus ID

2-s2.0-85097572983 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

Telomerase is a ribonucleoprotein complex that counteracts the shortening of chromosome ends due to incomplete replication. Telomerase contains a catalytic core of telomerase reverse transcriptase (TERT) and telomerase RNA (TER). However, what defines TERT and separates it from other reverse transcriptases remains a subject of debate. A recent cryoelectron microscopy map of Tetrahymena telomerase revealed the structure of a previously uncharacterized TERT domain (TRAP) with unanticipated interactions with the telomerase essential N-terminal (TEN) domain and roles in telomerase activity. Both TEN and TRAP are absent in the putative Tribolium TERT that has been used as a model for telomerase for over a decade. To investigate the conservation of TRAP and TEN across species, we performed multiple sequence alignments and statistical coupling analysis on all identified TERTs and find that TEN and TRAP have coevolved as telomerase-specific domains. Integrating the data from bioinformatic analysis and the structure of Tetrahymena telomerase, we built a pseudoatomic model of human telomerase catalytic core that accounts for almost all of the cryoelectron microscopy density in a published map, including TRAP in previously unassigned density as well as telomerase RNA domains essential for activity. This more complete model of the human telomerase catalytic core illustrates how domains of TER and TERT, including the TEN-TRAP complex, can interact in a conserved manner to regulate telomere synthesis.

Author List

Wang Y, Gallagher-Jones M, Sušac L, Song H, Feigon J

Author

Yaqiang Wang PhD, MS Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Binding Sites
Catalytic Domain
Cryoelectron Microscopy
Humans
Protein Binding
Protein Conformation
Protein Domains
RNA
Sequence Alignment
Structural Homology, Protein
Telomerase
Telomere-Binding Proteins
Tetrahymena thermophila
Tribolium