First atomic human telomerase model constructed
Telomeres, which are large structures of nucleoproteins that cover the ends chromosomes on eukaryotic cell membranes, are a type of nucleoprotein. A small part of the telomeres is lost when a cell divides due to the incomplete replication of the genome. Unchecked over time, the telomeres can reach a critical length, and the cell may face genomic instability, degradation or death. In order to counteract this shortening, a vital enzyme called telomerase synthesizes new telomeric repeats on the ends of chromosomes. Kelly Nguyen’s group at the LMB’s Structural Studies Division has solved the first atomic model for this enzyme. They also discovered a novel subunit of telomerase, a histone dimer.
Telomeres protect genetic information against degradation due to incomplete DNA replication. Telomeres also distinguish between the ends of natural chromosomes and DNA double-strand breaks to prevent an illicit DNA damage reaction. Telomeres are therefore essential to the maintenance of genome and chromosome integrity. Kelly’s previous cryo-EM research had revealed the composition and architecture of human telomerase holoenzyme with a resolution of 8 A (Angstroms). To understand the molecular mechanisms governing telomerase-mediated telomere preservation, a high resolution structure of the complex is required.
Kelly’s team, in collaboration Kathleen Collins from the University of California Berkeley and Rhiju das at Stanford University, prepared telomerase in cultured human cell cultures, then imaged it using cryo-EM, resulting in almost 44000 images. RELION, a computer program created at the LMB, was used to analyze the data in order to determine the 3.4-3.8A structure of telomerase. Kelly, Adam Fountain, Marike van Ron, George Ghanim and other members of Kelly’s group were able, from this data, to construct the first atomic model for telomerase. This included 12 subunits of protein and telomerase-RNA. The group completed the structure at such a high level of resolution that it was able to not only illuminate the common RNA and proteins motifs, but also highlight new interactions.
Source:
https://phys.org/news/2021-04-atomic-human-telomerase-electron-cryo-microscopy.html
