2yh0

From Proteopedia

(Difference between revisions)

Current revision

Solution structure of the closed conformation of human U2AF65 tandem RRM1 and RRM2 domains

Structural highlights

2yh0 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins.

Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF.,Mackereth CD, Madl T, Bonnal S, Simon B, Zanier K, Gasch A, Rybin V, Valcarcel J, Sattler M Nature. 2011 Jul 13;475(7356):408-11. doi: 10.1038/nature10171. PMID:21753750^[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
↑ Mackereth CD, Madl T, Bonnal S, Simon B, Zanier K, Gasch A, Rybin V, Valcarcel J, Sattler M. Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF. Nature. 2011 Jul 13;475(7356):408-11. doi: 10.1038/nature10171. PMID:21753750 doi:10.1038/nature10171

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2yh0"

@@ Line 1: / Line 1: @@
-[[Image:2yh0.jpg|left|200px]]
-<!--
+==Solution structure of the closed conformation of human U2AF65 tandem RRM1 and RRM2 domains==
-The line below this paragraph, containing "STRUCTURE_2yh0", creates the "Structure Box" on the page.
+<StructureSection load='2yh0' size='340' side='right'caption='[[2yh0]]' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2yh0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YH0 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
--->
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2yh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yh0 OCA], [https://pdbe.org/2yh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yh0 RCSB], [https://www.ebi.ac.uk/pdbsum/2yh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yh0 ProSAT]</span></td></tr>
-{{STRUCTURE_2yh0|  PDB=2yh0  |  SCENE=  }}
+</table>
+== Function ==
+[https://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 ==
+Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins.
-===SOLUTION STRUCTURE OF THE CLOSED CONFORMATION OF HUMAN U2AF65 TANDEM RRM1 AND RRM2 DOMAINS===
+Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF.,Mackereth CD, Madl T, Bonnal S, Simon B, Zanier K, Gasch A, Rybin V, Valcarcel J, Sattler M Nature. 2011 Jul 13;475(7356):408-11. doi: 10.1038/nature10171. PMID:21753750<ref>PMID:21753750</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-==About this Structure==
+</div>
-[[2yh0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YH0 OCA].
+<div class="pdbe-citations 2yh0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Gasch, A.]]
+[[Category: Large Structures]]
-[[Category: Mackereth, C D.]]
+[[Category: Gasch A]]
-[[Category: Madl, T.]]
+[[Category: Mackereth CD]]
-[[Category: Sattler, M.]]
+[[Category: Madl T]]
-[[Category: Simon, B.]]
+[[Category: Sattler M]]
-[[Category: Zanier, K.]]
+[[Category: Simon B]]
-[[Category: Mrna processing]]
+[[Category: Zanier K]]
-[[Category: Pre-mrna splicing]]
-[[Category: Rna binding protein]]
-[[Category: Transcription]]

2yh0

From Proteopedia

Current revision

Solution structure of the closed conformation of human U2AF65 tandem RRM1 and RRM2 domains

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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