Crystal structure of the endonuclease domain encoded by the telomere-specific long interspersed nuclear element, TRAS1

Abstract

The telomere-specific long interspersed nuclear element, TRAS1, encodes an endonuclease domain, TRAS1-EN, which specifically cleaves the telomeric repeat targets (TTAGG)n of insects and (TTAGGG)n of vertebrates. To elucidate the sequence-specific recognition properties of TRAS1-EN, we determined the crystal structure at 2.4-Å resolution. TRAS1-EN has a four-layered α/β sandwich structure; its topology is similar to apurinic/apyrimidinic endonucleases, but the β-hairpin (β 10-β11) at the edge of the DNA-binding surface makes an extra loop that distinguishes TRAS1-EN from cellular apurinic/apyrimidinic endonucleases. A protein-DNA complex model suggests that the β10-β11 hairpin fits into the minor groove, enabling interaction with the telomeric repeats. Mutational studies of TRAS1-EN also indicated that the Asp-130 and β10-β11 hairpin structure are involved in specific recognition of telomeric repeats.