5w0h: Difference between revisions
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==Structure of U2AF65 (U2AF2) RRM2 at 1.11 Angstrom Resolution== | |||
<StructureSection load='5w0h' size='340' side='right' caption='[[5w0h]], [[Resolution|resolution]] 1.11Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5w0h]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W0H FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5w0g|5w0g]]</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=5w0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0h OCA], [http://pdbe.org/5w0h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w0h RCSB], [http://www.ebi.ac.uk/pdbsum/5w0h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/U2AF2_HUMAN U2AF2_HUMAN]] Necessary for the splicing of pre-mRNA. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:15009664</ref> <ref>PMID:19470458</ref> <ref>PMID:19574390</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Acquired point mutations of pre-mRNA splicing factors recur among cancers, leukemias, and related neoplasms. Several studies have established that somatic mutations of a U2AF1 subunit, which normally recognizes 3' splice site junctions, recur among myelodysplastic syndromes. The U2AF2 splicing factor recognizes polypyrimidine signals that precede most 3' splice sites as a heterodimer with U2AF1. In contrast with those of the well-studied U2AF1 subunit, descriptions of cancer-relevant U2AF2 mutations and their structural relationships are lacking. Here, we survey databases of cancer-associated mutations and identify recurring missense mutations in the U2AF2 gene. We determine ultra-high-resolution structures of the U2AF2 RNA recognition motifs (RRM1 and RRM2) at 1.1 A resolution and map the structural locations of the mutated U2AF2 residues. Comparison with prior, lower-resolution structures of the tandem U2AF2 RRMs in the RNA-bound and apo states reveals clusters of cancer-associated mutations at the U2AF2 RRM-RNA or apo-RRM1-RRM2 interfaces. Although the role of U2AF2 mutations in malignant transformation remains uncertain, our results show that cancer-associated mutations correlate with functionally important surfaces of the U2AF2 splicing factor. | |||
Cancer-Associated Mutations Mapped on High-Resolution Structures of the U2AF2 RNA Recognition Motifs.,Glasser E, Agrawal AA, Jenkins JL, Kielkopf CL Biochemistry. 2017 Sep 12;56(36):4757-4761. doi: 10.1021/acs.biochem.7b00551., Epub 2017 Sep 1. PMID:28850223<ref>PMID:28850223</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5w0h" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Agrawal, A A]] | |||
[[Category: Jenkins, J L]] | |||
[[Category: Kielkopf, C L]] | |||
[[Category: Polypyrimidine tract]] | |||
[[Category: Rna binding protein]] | |||
[[Category: Rna binding protein-rna complex]] | |||
[[Category: Rna recognition motif]] | |||
[[Category: Rna splicing factor]] | |||