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2hzc

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Revision as of 15:31, 24 December 2014

Crystal structure of the N-terminal RRM of the U2AF large subunit

Structural highlights

2hzc is a 1 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2fzr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2g4b
Gene:	U2AF2, U2AF65 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The essential pre-mRNA splicing factor, U2 auxiliary factor 65KD (U2AF(65)) recognizes the polypyrimidine tract (Py-tract) consensus sequence of the pre-mRNA using two RNA recognition motifs (RRMs), the most prevalent class of eukaryotic RNA-binding domain. The Py-tracts of higher eukaryotic pre-mRNAs are often interrupted with purines, yet U2AF(65) must identify these degenerate Py-tracts for accurate pre-mRNA splicing. Previously, the structure of a U2AF(65) variant in complex with poly(U) RNA suggested that rearrangement of flexible side-chains or bound water molecules may contribute to degenerate Py-tract recognition by U2AF(65). Here, the X-ray structure of the N-terminal RRM domain of U2AF(65) (RRM1) is described at 1.47 A resolution in the absence of RNA. Notably, RNA-binding by U2AF(65) selectively stabilizes pre-existing alternative conformations of three side-chains located at the RNA interface (Arg150, Lys225, and Arg227). Additionally, a flexible loop connecting the beta2/beta3 strands undergoes a conformational change to interact with the RNA. These pre-existing alternative conformations may contribute to the ability of U2AF(65) to recognize a variety of Py-tract sequences. This rare, high-resolution view of an important member of the RRM class of RNA-binding domains highlights the role of alternative side-chain conformations in RNA recognition.

Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65) RNA recognition motif.,Thickman KR, Sickmier EA, Kielkopf CL J Mol Biol. 2007 Feb 23;366(3):703-10. Epub 2006 Dec 2. PMID:17188295^[4]

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

References

↑ Wang J, Gao QS, Wang Y, Lafyatis R, Stamm S, Andreadis A. Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. J Neurochem. 2004 Mar;88(5):1078-90. PMID:15009664
↑ Warf MB, Diegel JV, von Hippel PH, Berglund JA. The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9203-8. doi:, 10.1073/pnas.0900342106. Epub 2009 May 26. PMID:19470458 doi:10.1073/pnas.0900342106
↑ Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR 3rd, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Bottger A. Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science. 2009 Jul 3;325(5936):90-3. PMID:19574390 doi:325/5936/90
↑ Thickman KR, Sickmier EA, Kielkopf CL. Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65) RNA recognition motif. J Mol Biol. 2007 Feb 23;366(3):703-10. Epub 2006 Dec 2. PMID:17188295 doi:http://dx.doi.org/10.1016/j.jmb.2006.11.077

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/2hzc"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2hzc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2fzr 2fzr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HZC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HZC FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2g4b|2g4b]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2g4b|2g4b]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">U2AF2, U2AF65 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">U2AF2, U2AF65 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hzc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hzc RCSB], [http://www.ebi.ac.uk/pdbsum/2hzc PDBsum]</span></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=2hzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hzc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hzc RCSB], [http://www.ebi.ac.uk/pdbsum/2hzc PDBsum]</span></td></tr>
-<table>
+</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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 31: / Line 33: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Kielkopf, C L.]]
+[[Category: Kielkopf, C L]]
-[[Category: Sickmier, E A.]]
+[[Category: Sickmier, E A]]
-[[Category: Thickman, K R.]]
+[[Category: Thickman, K R]]
 [[Category: Alternative conformation]]
 [[Category: Rna binding protein]]

2hzc

From Proteopedia

Revision as of 15:31, 24 December 2014

Crystal structure of the N-terminal RRM of the U2AF large subunit

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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