Structural basis of the interaction between Topoisomerase IIIβ and the TDRD3 auxiliary factor

• Published in: Scientific reports 2017-02, Vol.7 (1), p.42123-42123, Article 42123
• Main Authors: Goto-Ito, Sakurako, Yamagata, Atsushi, Takahashi, Tomio S., Sato, Yusuke, Fukai, Shuya
• Format: Article
• Language: English
• Subjects: 631/45/173; 631/45/535/1266; 82; 82/16; 82/29; 82/83; Biochemistry, Molecular Biology; Humanities and Social Sciences; Life Sciences; multidisciplinary; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep42123

Topoisomerase IIIβ (TOP3β) is a DNA/RNA topoisomerase that has been implicated in epigenetic or translational control of gene expression. In cells, TOP3β co-exists with its specific auxiliary factor, TDRD3. TDRD3 serves as a scaffold protein to recruit TOP3β to its DNA/RNA substrates accumulating in specific cellular sites such as methylated chromatins or neural stress granules. Here we report the crystal structures of the catalytic domain of TOP3β, the DUF1767–OB-fold domains of TDRD3 and their complex at 3.44 Å, 1.62 Å and 3.6 Å resolutions, respectively. The toroidal-shaped catalytic domain of TOP3β binds the OB-fold domain of TDRD3. The TDRD3 OB-fold domain harbors the insertion loop, which is protruding from the core structure. Both the insertion loop and core region interact with TOP3β. Our pull-down binding assays showed that hydrophobic characters of the core surface and the amino- and carboxy-terminal regions of the insertion loop are essential for the interaction. Furthermore, by comparison with the structure of the homologous Topoisomerase IIIα (TOP3α)–RMI1 complex, we identified Arg96, Val109, Phe139 and the short insertion loop of TDRD3 as the critical structural elements for the specific interaction with TOP3β to avoid the non-cognate interaction with TOP3α.