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Article Name
Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).
Protein Name
Name: 2EZ6
Description (2EZ6) = A. aeolicus ribonuclease III
Number of Amino Acids in (2EZ6) = 218
Number of Nucleic Acids in (2EZ6) = 56
The Type of 2EZ6 PDB = dsRNA
RNA Dscription of (2EZ6) = Double Stranded RNA (dsRNA) Add scene
2EZ6 is the PDBID code for the Crystal structure of A. aeolicus RNaseIII-dsRBD in complex with dsRNA published in the article name listed under the artilce name and in Figure 6 of the original article.
Background Information
The PDB 2EZ6 is based on the crystal structure of the Crystal structure of A. aeolicus RNaseIII-dsRBD in complex with dsRNA published in the Article listed above and cited in figure 6 of the article. The major theme of this article was investigating the structural insights of the RNA-induced silencing complex (RISC), RISC assembly, which is facilitated by dsRNA-binding domains of human RNA helicase A (DHX9). RISC plays an important role as the key cellular machinery in RNAi pathways.Study showed that human RNA helicase A (DHX9) functions as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs).RISC is responsible for slicing or repressing the translation of the mRNA targets in a sequence-specific manner. The study further investigated the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs. The two binding domains dsRBD1 and dsRBD2, which stands for diuble stranded RNA binding domains and they are required for RISC association, and such association is mediated by dsRNA. The crystal structure analysis further revealed that the siRNA is recognized by RHA with the cooperation on dsRBDs.
The protein 2ez6 seems to be first discovered in the "Aquifex aeolicus" is a rod-shaped bacterium with a length of 2 to 6 micrometers and a diameter of around half a micrometer.The protein itself is a 2ez6 is a 4 chain structure with a sequence form.
Protein Function
Members of the ribonuclease III (RNase III) family are double-stranded RNA (dsRNA) specific endoribonucleases characterized by a signature motif in their active centers and a two-base 3' overhang in their products. While Dicer, which produces small interfering RNAs, is currently the focus of intense interest, the structurally simpler bacterial RNase III serves as a paradigm for the entire family. Here, we present the crystal structure of an RNase III-product complex, the first catalytic complex observed for the family. A 7 residue linker within the protein facilitates induced fit in protein-RNA recognition. A pattern of protein-RNA interactions, defined by four RNA binding motifs in RNase III and three protein-interacting boxes in dsRNA, is responsible for substrate specificity, while conserved amino acid residues and divalent cations are responsible for scissile-bond cleavage. The structure reveals a wealth of information about the mechanism of RNA hydrolysis that can be extrapolated to other RNase III family members.
Relevance
The major importance of the PDB 2EZ6 is that it is part of the RISC assembly, which codes for RNA silencing. RNA silencing refers to a conserved sequence-specific gene regulation mechanism mediated by small RNA molecules. RNA silencing plays a fundamental role in many important biological processes in eukaryotes, including host gene regulation and defense against invading foreign nucleic acids.More specifically the application of this protein is integral small RNA processing and small RNA-mediated gene regulation. Both RNA processimng and gene regulation are important factors of gene therapy, preventing viral and cancerous mutations in the human body.
Structural Highlights
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References
1. Fu, Qinqin, and Y. Adam Yuan. "Structural Insights into RISC Assembly Facilitated by DsRNA-binding Domains of Human RNA Helicase A (DHX9) | Nucleic Acids Research | Oxford Academic." OUP Academic. Oxford University Press, 29 Jan. 2013. Web. 08 Oct. 2017.
2.Gan, J., J. E. Tropea, B. P. Austin, D. L. Court, D. S. Waugh, and X. Ji. "Structural Insight into the Mechanism of Double-stranded RNA Processing by Ribonuclease III." Cell. U.S. National Library of Medicine, 27 Jan. 2006. Web. 08 Oct. 2017.
