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5m8i

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Revision as of 13:09, 10 May 2019

Solution structure of CUG-BP2 RRM3 in complex with 5'-UUUAA-3' RNA

Structural highlights

5m8i is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CELF2, BRUNOL3, CUGBP2, ETR3, NAPOR (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CELF2_HUMAN] RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of TNNT2 in embryonic, but not adult, skeletal muscle. Activates TNNT2 exon 5 inclusion by antagonizing the repressive effect of PTB. Acts as both an activator and repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Promotes inclusion of exonS 21 and exclusion of exon 5 of the NMDA receptor R1 pre-mRNA. Involved in the apoB RNA editing activity. Increases COX2 mRNA stability and inhibits COX2 mRNA translation in epithelial cells after radiation injury (By similarity). Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression (By similarity). Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK. Binds to the muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5. Binds preferentially to UG-rich sequences, in particular UG repeat and UGUU motifs. Binds to apoB mRNA, specifically to AU-rich sequences located immediatly upstream of the edited cytidine. Binds AU-rich sequences in the 3'-UTR of COX2 mRNA (By similarity). Binds to an intronic RNA element responsible for the silencing of exon 21 splicing (By similarity). Binds to (CUG)n repeats (By similarity).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3' untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5'-UUUAA-3' originating from the COX-2 3'-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high- or low-affinity binding with functional implications. This study highlights a mechanism for RNA discrimination possibly common to multiple RRMs as several prominent members display a similar rearrangement of aromatic residues upon binding their targets.The RNA Recognition Motif (RRM) is the most ubiquitous RNA binding domain. Here the authors combined NMR and molecular dynamics simulations and show that the RRM RNA binding surface exists in different states and that a conformational switch of aromatic side-chains fine-tunes sequence specific binding affinities.

Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination.,Diarra Dit Konte N, Krepl M, Damberger FF, Ripin N, Duss O, Sponer J, Allain FH Nat Commun. 2017 Sep 21;8(1):654. doi: 10.1038/s41467-017-00631-3. PMID:28935965^[8]

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

References

↑ Anant S, Henderson JO, Mukhopadhyay D, Navaratnam N, Kennedy S, Min J, Davidson NO. Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor. J Biol Chem. 2001 Dec 14;276(50):47338-51. Epub 2001 Sep 27. PMID:11577082 doi:http://dx.doi.org/10.1074/jbc.M104911200
↑ Ladd AN, Charlet N, Cooper TA. The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing. Mol Cell Biol. 2001 Feb;21(4):1285-96. PMID:11158314 doi:10.1128/MCB.21.4.1285-1296.2001
↑ Charlet-B N, Logan P, Singh G, Cooper TA. Dynamic antagonism between ETR-3 and PTB regulates cell type-specific alternative splicing. Mol Cell. 2002 Mar;9(3):649-58. PMID:11931771
↑ Gromak N, Matlin AJ, Cooper TA, Smith CW. Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein. RNA. 2003 Apr;9(4):443-56. PMID:12649496
↑ Singh G, Charlet-B N, Han J, Cooper TA. ETR-3 and CELF4 protein domains required for RNA binding and splicing activity in vivo. Nucleic Acids Res. 2004 Feb 18;32(3):1232-41. Print 2004. PMID:14973222 doi:http://dx.doi.org/10.1093/nar/gkh275
↑ Faustino NA, Cooper TA. Identification of putative new splicing targets for ETR-3 using sequences identified by systematic evolution of ligands by exponential enrichment. Mol Cell Biol. 2005 Feb;25(3):879-87. PMID:15657417 doi:http://dx.doi.org/10.1128/MCB.25.3.879-887.2005
↑ Han J, Cooper TA. Identification of CELF splicing activation and repression domains in vivo. Nucleic Acids Res. 2005 May 13;33(9):2769-80. Print 2005. PMID:15894795 doi:http://dx.doi.org/10.1093/nar/gki561
↑ Diarra Dit Konte N, Krepl M, Damberger FF, Ripin N, Duss O, Sponer J, Allain FH. Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination. Nat Commun. 2017 Sep 21;8(1):654. doi: 10.1038/s41467-017-00631-3. PMID:28935965 doi:http://dx.doi.org/10.1038/s41467-017-00631-3

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/5m8i"

@@ Line 1: / Line 1: @@
 ==Solution structure of CUG-BP2 RRM3 in complex with 5'-UUUAA-3' RNA==
-<StructureSection load='5m8i' size='340' side='right' caption='[[5m8i]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='5m8i' size='340' side='right'caption='[[5m8i]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5m8i]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M8I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5m8i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M8I FirstGlance]. <br>
-</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=5m8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m8i OCA], [http://pdbe.org/5m8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m8i RCSB], [http://www.ebi.ac.uk/pdbsum/5m8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m8i ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CELF2, BRUNOL3, CUGBP2, ETR3, NAPOR ([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=5m8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m8i OCA], [http://pdbe.org/5m8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m8i RCSB], [http://www.ebi.ac.uk/pdbsum/5m8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m8i ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Allain, F H.T]]
 [[Category: Damberger, F F]]

5m8i

From Proteopedia

Revision as of 13:09, 10 May 2019

Solution structure of CUG-BP2 RRM3 in complex with 5'-UUUAA-3' RNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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