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| | <StructureSection load='5oc6' size='340' side='right'caption='[[5oc6]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='5oc6' size='340' side='right'caption='[[5oc6]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oc6]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OC6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OC6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oc6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OC6 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUS2, DUS2L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5oc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oc6 OCA], [http://pdbe.org/5oc6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oc6 RCSB], [http://www.ebi.ac.uk/pdbsum/5oc6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oc6 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5oc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oc6 OCA], [https://pdbe.org/5oc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oc6 RCSB], [https://www.ebi.ac.uk/pdbsum/5oc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oc6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DUS2L_HUMAN DUS2L_HUMAN]] Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.<ref>PMID:15994936</ref> <ref>PMID:18096616</ref> | + | [https://www.uniprot.org/uniprot/DUS2L_HUMAN DUS2L_HUMAN] Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.<ref>PMID:15994936</ref> <ref>PMID:18096616</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bou-nader, C]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Hamdane, D]] | + | [[Category: Bou-nader C]] |
| - | [[Category: Pecqueur, L]] | + | [[Category: Hamdane D]] |
| - | [[Category: Double-stranded rna-binding domain protein-rna complex dsrna]]
| + | [[Category: Pecqueur L]] |
| - | [[Category: Rna binding protein]]
| + | |
| Structural highlights
Function
DUS2L_HUMAN Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.[1] [2]
Publication Abstract from PubMed
Double stranded RNA-binding domain (dsRBD) is a ubiquitous domain specialized in the recognition of double-stranded RNAs (dsRNAs). Present in many proteins and enzymes involved in various functional roles of RNA metabolism, including RNA splicing, editing, and transport, dsRBD generally binds to RNAs that lack complex structures. However, this belief has recently been challenged by the discovery of a dsRBD serving as a major tRNA binding module for human dihydrouridine synthase 2 (hDus2), a flavoenzyme that catalyzes synthesis of dihydrouridine within the complex elbow structure of tRNA. We here unveil the molecular mechanism by which hDus2 dsRBD recognizes a tRNA ligand. By solving the crystal structure of this dsRBD in complex with a dsRNA together with extensive characterizations of its interaction with tRNA using mutagenesis, NMR and SAXS, we establish that while hDus2 dsRBD retains a conventional dsRNA recognition capability, the presence of an N-terminal extension appended to the canonical domain provides additional residues for binding tRNA in a structure-specific mode of action. Our results support that this extension represents a feature by which the dsRBD specializes in tRNA biology and more broadly highlight the importance of structural appendages to canonical domains in promoting the emergence of functional diversity.
Molecular basis for transfer RNA recognition by the double-stranded RNA-binding domain of human dihydrouridine synthase 2.,Bou-Nader C, Barraud P, Pecqueur L, Perez J, Velours C, Shepard W, Fontecave M, Tisne C, Hamdane D Nucleic Acids Res. 2019 Jan 3. pii: 5271498. doi: 10.1093/nar/gky1302. PMID:30605527[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T, Miyamoto M, Kondo S, Nakamura Y. A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis. Cancer Res. 2005 Jul 1;65(13):5638-46. PMID:15994936 doi:http://dx.doi.org/65/13/5638
- ↑ Mittelstadt M, Frump A, Khuu T, Fowlkes V, Handy I, Patel CV, Patel RC. Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR. Nucleic Acids Res. 2008 Feb;36(3):998-1008. Epub 2007 Dec 20. PMID:18096616 doi:http://dx.doi.org/10.1093/nar/gkm1129
- ↑ Bou-Nader C, Barraud P, Pecqueur L, Perez J, Velours C, Shepard W, Fontecave M, Tisne C, Hamdane D. Molecular basis for transfer RNA recognition by the double-stranded RNA-binding domain of human dihydrouridine synthase 2. Nucleic Acids Res. 2019 Jan 3. pii: 5271498. doi: 10.1093/nar/gky1302. PMID:30605527 doi:http://dx.doi.org/10.1093/nar/gky1302
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