Structural basis of the interaction between Topoisomerase III? and the TDRD3 auxiliary factor.

ABSTRACT: Topoisomerase III? (TOP3?) is a DNA/RNA topoisomerase that has been implicated in epigenetic or translational control of gene expression. In cells, TOP3? co-exists with its specific auxiliary factor, TDRD3. TDRD3 serves as a scaffold protein to recruit TOP3? 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 TOP3?, 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 TOP3? 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 TOP3?. 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 III? (TOP3?)-RMI1 complex, we identified Arg96, Val109, Phe139 and the short insertion loop of TDRD3 as the critical structural elements for the specific interaction with TOP3? to avoid the non-cognate interaction with TOP3?.

SUBMITTER: Goto-Ito S 

PROVIDER: S-EPMC5296760 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature