Integrative structural biology of Tetrahymena telomerase – insights into catalytic mechanism and interaction at telomeres

Telomerase is a ribonucleoprotein complex that helps maintain telomeres, the physical ends of linear chromosomes. The low cellular levels of telomerase, propensity for telomerase reverse transcriptase and other telomerase proteins to aggregate, and cell cycle regulation of telomerase assembly in most organisms has made it a challenging complex for structural biology. Here we review recent progress in determining the structural basis of Tetrahymena telomerase holoenzyme function and interaction at telomeres from solution NMR, X-ray crystallography and electron microscopy studies, including the first cryoelectron microscopy structure of a telomerase holoenzyme (Science, 350, 2015, aab4070).