5syb

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==Crystal structure of human PHF5A==
==Crystal structure of human PHF5A==
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<StructureSection load='5syb' size='340' side='right' caption='[[5syb]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
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<StructureSection load='5syb' size='340' side='right'caption='[[5syb]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5syb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYB FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5syb]] 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=5SYB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SYB FirstGlance]. <br>
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</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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82&#8491;</td></tr>
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<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=5syb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syb OCA], [http://pdbe.org/5syb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syb RCSB], [http://www.ebi.ac.uk/pdbsum/5syb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syb ProSAT]</span></td></tr>
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<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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5syb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syb OCA], [https://pdbe.org/5syb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5syb RCSB], [https://www.ebi.ac.uk/pdbsum/5syb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5syb ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/PHF5A_HUMAN PHF5A_HUMAN]] Acts as a transcriptional regulator by binding to the GJA1/Cx43 promoter and enhancing its up-regulation by ESR1/ER-alpha. Also involved in pre-mRNA splicing.<ref>PMID:12234937</ref>
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[https://www.uniprot.org/uniprot/PHF5A_HUMAN PHF5A_HUMAN] Acts as a transcriptional regulator by binding to the GJA1/Cx43 promoter and enhancing its up-regulation by ESR1/ER-alpha. Also involved in pre-mRNA splicing.<ref>PMID:12234937</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Pladienolide, herboxidiene and spliceostatin have been identified as splicing modulators that target SF3B1 in the SF3b subcomplex. Here we report that PHF5A, another component of this subcomplex, is also targeted by these compounds. Mutations in PHF5A-Y36, SF3B1-K1071, SF3B1-R1074 and SF3B1-V1078 confer resistance to these modulators, suggesting a common interaction site. RNA-seq analysis reveals that PHF5A-Y36C has minimal effect on basal splicing but inhibits the global action of splicing modulators. Moreover, PHF5A-Y36C alters splicing modulator-induced intron-retention/exon-skipping profile, which correlates with the differential GC content between adjacent introns and exons. We determine the crystal structure of human PHF5A demonstrating that Y36 is located on a highly conserved surface. Analysis of the cryo-EM spliceosome Bact complex shows that the resistance mutations cluster in a pocket surrounding the branch point adenosine, suggesting a competitive mode of action. Collectively, we propose that PHF5A-SF3B1 forms a central node for binding to these splicing modulators.
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Splicing modulators act at the branch point adenosine binding pocket defined by the PHF5A-SF3b complex.,Teng T, Tsai JH, Puyang X, Seiler M, Peng S, Prajapati S, Aird D, Buonamici S, Caleb B, Chan B, Corson L, Feala J, Fekkes P, Gerard B, Karr C, Korpal M, Liu X, T Lowe J, Mizui Y, Palacino J, Park E, Smith PG, Subramanian V, Wu ZJ, Zou J, Yu L, Chicas A, Warmuth M, Larsen N, Zhu P Nat Commun. 2017 May 25;8:15522. doi: 10.1038/ncomms15522. PMID:28541300<ref>PMID:28541300</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5syb" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Fekkes, P]]
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[[Category: Homo sapiens]]
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[[Category: Larsen, N A]]
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[[Category: Large Structures]]
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[[Category: Teng, T]]
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[[Category: Fekkes P]]
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[[Category: Tsai, J H.C]]
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[[Category: Larsen NA]]
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[[Category: Zhu, P]]
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[[Category: Teng T]]
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[[Category: Core component]]
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[[Category: Tsai JHC]]
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[[Category: Human spliceosome]]
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[[Category: Zhu P]]
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[[Category: Sf3b complex]]
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[[Category: Transcription]]
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Current revision

Crystal structure of human PHF5A

PDB ID 5syb

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