5gve
From Proteopedia
Human TOP3B-TDRD3 complex
Structural highlights
Function[TOP3B_HUMAN] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand than undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Possesses negatively supercoiled DNA relaxing activity. [TDRD3_HUMAN] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.[1] [2] [3] Publication Abstract from PubMedTopoisomerase IIIbeta (TOP3beta) is a DNA/RNA topoisomerase that has been implicated in epigenetic or translational control of gene expression. In cells, TOP3beta co-exists with its specific auxiliary factor, TDRD3. TDRD3 serves as a scaffold protein to recruit TOP3beta 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 TOP3beta, the DUF1767-OB-fold domains of TDRD3 and their complex at 3.44 A, 1.62 A and 3.6 A resolutions, respectively. The toroidal-shaped catalytic domain of TOP3beta 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 TOP3beta. 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 IIIalpha (TOP3alpha)-RMI1 complex, we identified Arg96, Val109, Phe139 and the short insertion loop of TDRD3 as the critical structural elements for the specific interaction with TOP3beta to avoid the non-cognate interaction with TOP3alpha. Structural basis of the interaction between Topoisomerase IIIbeta and the TDRD3 auxiliary factor.,Goto-Ito S, Yamagata A, Takahashi TS, Sato Y, Fukai S Sci Rep. 2017 Feb 8;7:42123. doi: 10.1038/srep42123. PMID:28176834[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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