Premium
Crystal structure of a tankyrase 1–telomere repeat factor 1 complex
Author(s) -
Li Bo,
Qiao Ruihong,
Wang Zhizhi,
Zhou Weihong,
Li Xin,
Xu Wenqing,
Rao Zihe
Publication year - 2016
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x16004131
Subject(s) - telomere , shelterin , ankyrin repeat , telomerase , telomere binding protein , protein subunit , cellular aging , crystallography , chemistry , microbiology and biotechnology , biology , dna , dna binding protein , biochemistry , transcription factor , gene
Telomere repeat factor 1 (TRF1) is a subunit of shelterin (also known as the telosome) and plays a critical role in inhibiting telomere elongation by telomerase. Tankyrase 1 (TNKS1) is a poly(ADP‐ribose) polymerase that regulates the activity of TRF1 through poly(ADP‐ribosyl)ation (PARylation). PARylation of TRF1 by TNKS1 leads to the release of TRF1 from telomeres and allows telomerase to access telomeres. The interaction between TRF1 and TNKS1 is thus important for telomere stability and the mitotic cell cycle. Here, the crystal structure of a complex between the N‐terminal acidic domain of TRF1 (residues 1–55) and a fragment of TNKS1 covering the second and third ankyrin‐repeat clusters (ARC2‐3) is presented at 2.2 Å resolution. The TNKS1–TRF1 complex crystals were optimized using an `oriented rescreening' strategy, in which the initial crystallization condition was used as a guide for a second round of large‐scale sparse‐matrix screening. This crystallographic and biochemical analysis provides a better understanding of the TRF1–TNKS1 interaction and the three‐dimensional structure of the ankyrin‐repeat domain of TNKS.