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New page: left|200px<br /> <applet load="2hgn" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hgn" /> '''NMR structure of the third qRRM domain of h...
 
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[[Image:2hgn.gif|left|200px]]<br />
<applet load="2hgn" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2hgn" />
'''NMR structure of the third qRRM domain of human hnRNP F'''<br />


==Overview==
==NMR structure of the third qRRM domain of human hnRNP F==
The heterogeneous nuclear ribonucleoprotein (hnRNP) F belongs to the hnRNP, H family involved in the regulation of alternative splicing and, polyadenylation and specifically recognizes poly(G) sequences (G-tracts)., In particular, hnRNP F binds a G-tract of the Bcl-x RNA and regulates its, alternative splicing, leading to two isoforms, Bcl-x(S) and Bcl-x(L), with, antagonist functions. In order to gain insight into G-tract recognition by, hnRNP H members, we initiated an NMR study of human hnRNP F. We present, the solution structure of the three quasi RNA recognition motifs (qRRMs), of hnRNP F and identify the residues that are important for the, interaction with the Bcl-x RNA by NMR chemical shift perturbation and, mutagenesis experiments. The three qRRMs exhibit the canonical, betaalphabetabetaalphabeta RRM fold but additional secondary structure, elements are present in the two N-terminal qRRMs of hnRNP F. We show that, qRRM1 and qRRM2 but not qRRM3 are responsible for G-tract recognition and, that the residues of qRRM1 and qRRM2 involved in G-tract interaction are, not on the beta-sheet surface as observed for the classical RRM but are, part of a short beta-hairpin and two adjacent loops. These regions define, a novel interaction surface for RNA recognition by RRMs.
<StructureSection load='2hgn' size='340' side='right'caption='[[2hgn]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hgn]] 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=2HGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HGN FirstGlance]. <br>
</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=2hgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hgn OCA], [https://pdbe.org/2hgn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hgn RCSB], [https://www.ebi.ac.uk/pdbsum/2hgn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hgn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HNRPF_HUMAN HNRPF_HUMAN] Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state.<ref>PMID:20526337</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hg/2hgn_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hgn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The heterogeneous nuclear ribonucleoprotein (hnRNP) F belongs to the hnRNP H family involved in the regulation of alternative splicing and polyadenylation and specifically recognizes poly(G) sequences (G-tracts). In particular, hnRNP F binds a G-tract of the Bcl-x RNA and regulates its alternative splicing, leading to two isoforms, Bcl-x(S) and Bcl-x(L), with antagonist functions. In order to gain insight into G-tract recognition by hnRNP H members, we initiated an NMR study of human hnRNP F. We present the solution structure of the three quasi RNA recognition motifs (qRRMs) of hnRNP F and identify the residues that are important for the interaction with the Bcl-x RNA by NMR chemical shift perturbation and mutagenesis experiments. The three qRRMs exhibit the canonical betaalphabetabetaalphabeta RRM fold but additional secondary structure elements are present in the two N-terminal qRRMs of hnRNP F. We show that qRRM1 and qRRM2 but not qRRM3 are responsible for G-tract recognition and that the residues of qRRM1 and qRRM2 involved in G-tract interaction are not on the beta-sheet surface as observed for the classical RRM but are part of a short beta-hairpin and two adjacent loops. These regions define a novel interaction surface for RNA recognition by RRMs.


==About this Structure==
NMR structure of the three quasi RNA recognition motifs (qRRMs) of human hnRNP F and interaction studies with Bcl-x G-tract RNA: a novel mode of RNA recognition.,Dominguez C, Allain FH Nucleic Acids Res. 2006 Aug 2;34(13):3634-45. Print 2006. PMID:16885237<ref>PMID:16885237</ref>
2HGN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HGN OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
NMR structure of the three quasi RNA recognition motifs (qRRMs) of human hnRNP F and interaction studies with Bcl-x G-tract RNA: a novel mode of RNA recognition., Dominguez C, Allain FH, Nucleic Acids Res. 2006 Aug 2;34(13):3634-45. Print 2006. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16885237 16885237]
</div>
<div class="pdbe-citations 2hgn" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Allain, F.H.T.]]
[[Category: Allain FH-T]]
[[Category: Dominguez, C.]]
[[Category: Dominguez C]]
[[Category: alternative splicing]]
[[Category: g-quadruplex]]
[[Category: g-tract]]
[[Category: rna recognition motif]]
 
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