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5ifm

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Revision as of 08:04, 8 January 2020

Human NONO (p54nrb) Homodimer

Structural highlights

5ifm is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	NONO, NRB54 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Non-POU domain-containing octamer-binding protein (NONO, a.k.a. p54(nrb)) is a central player in nuclear gene regulation with rapidly emerging medical significance. NONO is a member of the highly conserved Drosophila behaviour/human splicing (DBHS) protein family, a dynamic family of obligatory dimeric nuclear regulatory mediators. However, work with the NONO homodimer has been limited by rapid irreversible sample aggregation. Here, it is reported that L-proline stabilizes purified NONO homodimers, enabling good-quality solution small-angle X-ray structure determination and crystallization. NONO crystallized in the apparent space group P21 with a unique axis (b) of 408.9 A and with evidence of twinning, as indicated by the cumulative intensity distribution L statistic, suggesting the possibility of space group P1. Structure solution by molecular replacement shows a superhelical arrangement of six NONO homodimers (or 12 in P1) oriented parallel to the long axis, resulting in extensive noncrystallographic symmetry. Further analysis revealed that the crystal was not twinned, but the collected data suffered from highly overlapping reflections that obscured the L-test. Optimized data collection on a new crystal using higher energy X-rays, a smaller beam width and an increased sample-to-detector distance produced non-overlapping reflections to 2.6 A resolution. The steps taken to analyse and overcome this series of practical difficulties and to produce a biologically informative structure are discussed.

A crystallographic study of human NONO (p54(nrb)): overcoming pathological problems with purification, data collection and noncrystallographic symmetry.,Knott GJ, Panjikar S, Thorn A, Fox AH, Conte MR, Lee M, Bond CS Acta Crystallogr D Struct Biol. 2016 Jun;72(Pt 6):761-9. doi:, 10.1107/S2059798316005830. Epub 2016 May 25. PMID:27303796^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Straub T, Knudsen BR, Boege F. PSF/p54(nrb) stimulates "jumping" of DNA topoisomerase I between separate DNA helices. Biochemistry. 2000 Jun 27;39(25):7552-8. PMID:10858305
↑ Zhang Z, Carmichael GG. The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell. 2001 Aug 24;106(4):465-75. PMID:11525732
↑ Sewer MB, Nguyen VQ, Huang CJ, Tucker PW, Kagawa N, Waterman MR. Transcriptional activation of human CYP17 in H295R adrenocortical cells depends on complex formation among p54(nrb)/NonO, protein-associated splicing factor, and SF-1, a complex that also participates in repression of transcription. Endocrinology. 2002 Apr;143(4):1280-90. PMID:11897684 doi:http://dx.doi.org/10.1210/endo.143.4.8748
↑ Bladen CL, Udayakumar D, Takeda Y, Dynan WS. Identification of the polypyrimidine tract binding protein-associated splicing factor.p54(nrb) complex as a candidate DNA double-strand break rejoining factor. J Biol Chem. 2005 Feb 18;280(7):5205-10. Epub 2004 Dec 7. PMID:15590677 doi:http://dx.doi.org/10.1074/jbc.M412758200
↑ Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS. Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci U S A. 2012 Mar 13. PMID:22416126 doi:10.1073/pnas.1120792109
↑ Knott GJ, Panjikar S, Thorn A, Fox AH, Conte MR, Lee M, Bond CS. A crystallographic study of human NONO (p54(nrb)): overcoming pathological problems with purification, data collection and noncrystallographic symmetry. Acta Crystallogr D Struct Biol. 2016 Jun;72(Pt 6):761-9. doi:, 10.1107/S2059798316005830. Epub 2016 May 25. PMID:27303796 doi:http://dx.doi.org/10.1107/S2059798316005830

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ifm"

@@ Line 1: / Line 1: @@
 ==Human NONO (p54nrb) Homodimer==
-<StructureSection load='5ifm' size='340' side='right' caption='[[5ifm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+<StructureSection load='5ifm' size='340' side='right'caption='[[5ifm]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ifm]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IFM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IFM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ifm]] is a 12 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=5IFM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IFM FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NONO, NRB54 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5ifm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ifm OCA], [http://pdbe.org/5ifm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ifm RCSB], [http://www.ebi.ac.uk/pdbsum/5ifm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ifm ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bond, C S]]
 [[Category: Knott, G J]]
 [[Category: Dbhs protein rna binding]]
 [[Category: Rna binding protein]]

5ifm

From Proteopedia

Revision as of 08:04, 8 January 2020

Human NONO (p54nrb) Homodimer

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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