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| | ==Crystal structure of a paraspeckle-protein heterodimer, PSPC1/NONO== | | ==Crystal structure of a paraspeckle-protein heterodimer, PSPC1/NONO== |
| - | <StructureSection load='3sde' size='340' side='right' caption='[[3sde]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3sde' size='340' side='right'caption='[[3sde]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3sde]] is a 2 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=3SDE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SDE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3sde]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SDE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SDE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PSPC1, PSP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NONO, NRB54 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=3sde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sde OCA], [http://pdbe.org/3sde PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sde RCSB], [http://www.ebi.ac.uk/pdbsum/3sde PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sde 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=3sde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sde OCA], [https://pdbe.org/3sde PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sde RCSB], [https://www.ebi.ac.uk/pdbsum/3sde PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sde ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/NONO_HUMAN NONO_HUMAN]] Translocation renal cell carcinoma. A chromosomal aberration involving NONO may be a cause of papillary renal cell carcinoma (PRCC). Translocation t(X;X)(p11.2;q13.1) with TFE3. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PSPC1_HUMAN PSPC1_HUMAN]] Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line (By similarity). Binds to poly(A), poly(G) and poly(U) RNA homopolymers (By similarity). Together with NONO, required for the formation of nuclear paraspeckles.<ref>PMID:22416126</ref> [[http://www.uniprot.org/uniprot/NONO_HUMAN NONO_HUMAN]] DNA- and RNA binding protein, involved in several nuclear processes. Binds the conventional octamer sequence in double-stranded DNA. Also binds single-stranded DNA and RNA at a site independent of the duplex site. Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. Together with PSPC1, required for the formation of nuclear paraspeckles. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1. The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends. In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional avtivity. NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.<ref>PMID:10858305</ref> <ref>PMID:11525732</ref> <ref>PMID:11897684</ref> <ref>PMID:15590677</ref> <ref>PMID:22416126</ref> | + | [https://www.uniprot.org/uniprot/PSPC1_HUMAN PSPC1_HUMAN] Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line (By similarity). Binds to poly(A), poly(G) and poly(U) RNA homopolymers (By similarity). Together with NONO, required for the formation of nuclear paraspeckles.<ref>PMID:22416126</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Proteins of the Drosophila behavior/human splicing (DBHS) family include mammalian SFPQ (PSF), NONO (p54nrb), PSPC1, and invertebrate NONA and Hrp65. DBHS proteins are predominately nuclear, and are involved in transcriptional and posttranscriptional gene regulatory functions as well as DNA repair. DBHS proteins influence a wide gamut of biological processes, including the regulation of circadian rhythm, carcinogenesis, and progression of cancer. Additionally, mammalian DBHS proteins associate with the architectural long noncoding RNA NEAT1 (Menepsilon/beta) to form paraspeckles, subnuclear bodies that alter gene expression via the nuclear retention of RNA. Here we describe the crystal structure of the heterodimer of the multidomain conserved region of the DBHS proteins, PSPC1 and NONO. These proteins form an extensively intertwined dimer, consistent with the observation that the different DBHS proteins are typically copurified from mammalian cells, and suggesting that they act as obligate heterodimers. The PSPC1/NONO heterodimer has a right-handed antiparallel coiled-coil that positions two of four RNA recognition motif domains in an unprecedented arrangement on either side of a 20-A channel. This configuration is supported by a protein:protein interaction involving the NONA/paraspeckle domain, which is characteristic of the DBHS family. By examining various mutants and truncations in cell culture, we find that DBHS proteins require an additional antiparallel coiled-coil emanating from either end of the dimer for paraspeckle subnuclear body formation. These results suggest that paraspeckles may potentially form through self-association of DBHS dimers into higher-order structures.
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| - | Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation.,Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS Proc Natl Acad Sci U S A. 2012 Mar 13. PMID:22416126<ref>PMID:22416126</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3sde" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bond, C S]] | + | [[Category: Large Structures]] |
| - | [[Category: Lee, M]] | + | [[Category: Bond CS]] |
| - | [[Category: Passon, D M]] | + | [[Category: Lee M]] |
| - | [[Category: Anti parallel right handed coiled-coil]] | + | [[Category: Passon DM]] |
| - | [[Category: Dbh]]
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| - | [[Category: Long non-coding rna]]
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| - | [[Category: Mrna]]
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| - | [[Category: Nop]]
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| - | [[Category: Nucleus]]
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| - | [[Category: Paraspeckle]]
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| - | [[Category: Rna binding]]
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| - | [[Category: Rna binding protein]]
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| - | [[Category: Rrm]]
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