5kw1
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of the Two Tandem RRM Domains of PUF60 Bound to a Modified AdML Pre-mRNA 3' Splice Site Analogue== | |
| + | <StructureSection load='5kw1' size='340' side='right' caption='[[5kw1]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5kw1]] 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=5KW1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KW1 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></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DU:2-DEOXYURIDINE-5-MONOPHOSPHATE'>DU</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kwd|5kwd]], [[5kw6|5kw6]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PUF60, FIR, ROBPI, SIAHBP1 ([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=5kw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kw1 OCA], [http://pdbe.org/5kw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kw1 RCSB], [http://www.ebi.ac.uk/pdbsum/5kw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kw1 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PUF60_HUMAN PUF60_HUMAN]] DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA.<ref>PMID:10882074</ref> <ref>PMID:10606266</ref> <ref>PMID:11239393</ref> <ref>PMID:16452196</ref> <ref>PMID:16628215</ref> <ref>PMID:17579712</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | c-myc is essential for cell homeostasis and growth but lethal if improperly regulated. Transcription of this oncogene is governed by the counterbalancing forces of two proteins on TFIIH--the FUSE binding protein (FBP) and the FBP-interacting repressor (FIR). FBP and FIR recognize single-stranded DNA upstream of the P1 promoter, known as FUSE, and influence transcription by oppositely regulating TFIIH at the promoter site. Size exclusion chromatography coupled with light scattering reveals that an FIR dimer binds one molecule of single-stranded DNA. The crystal structure confirms that FIR binds FUSE as a dimer, and only the N-terminal RRM domain participates in nucleic acid recognition. Site-directed mutations of conserved residues in the first RRM domain reduce FIR's affinity for FUSE, while analogous mutations in the second RRM domain either destabilize the protein or have no effect on DNA binding. Oppositely oriented DNA on parallel binding sites of the FIR dimer results in spooling of a single strand of bound DNA, and suggests a mechanism for c-myc transcriptional control. | ||
| - | + | Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c-myc inhibition.,Crichlow GV, Zhou H, Hsiao HH, Frederick KB, Debrosse M, Yang Y, Folta-Stogniew EJ, Chung HJ, Fan C, De la Cruz EM, Levens D, Lolis E, Braddock D EMBO J. 2008 Jan 9;27(1):277-89. Epub 2007 Dec 6. PMID:18059478<ref>PMID:18059478</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5kw1" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Albright, R]] | [[Category: Albright, R]] | ||
| + | [[Category: Braddock, D T]] | ||
| + | [[Category: Crichlow, G V]] | ||
| + | [[Category: Hsiao, H H]] | ||
| + | [[Category: Lolis, E J]] | ||
| + | [[Category: Protein-nucleic acid complex]] | ||
| + | [[Category: Splicing factor]] | ||
| + | [[Category: Splicing-dna complex]] | ||
| + | [[Category: Tandem rrm]] | ||
Revision as of 20:55, 15 November 2017
Crystal Structure of the Two Tandem RRM Domains of PUF60 Bound to a Modified AdML Pre-mRNA 3' Splice Site Analogue
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