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| | ==RRM domain of mRNA export adaptor REF2-I bound to HVS ORF57 peptide== | | ==RRM domain of mRNA export adaptor REF2-I bound to HVS ORF57 peptide== |
| - | <StructureSection load='2yka' size='340' side='right' caption='[[2yka]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2yka' size='340' side='right'caption='[[2yka]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2yka]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Herpesvirus_saimiri Herpesvirus saimiri] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YKA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YKA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2yka]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Saimiriine_gammaherpesvirus_2 Saimiriine gammaherpesvirus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YKA FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f3j|2f3j]]</td></tr> | + | </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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2yka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yka OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yka RCSB], [http://www.ebi.ac.uk/pdbsum/2yka PDBsum]</span></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=2yka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yka OCA], [https://pdbe.org/2yka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yka RCSB], [https://www.ebi.ac.uk/pdbsum/2yka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yka ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ALRF2_MOUSE ALRF2_MOUSE]] Export adapter involved in spliced and unspliced mRNA nuclear export. Binds mRNA which is transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway); enhances NXF1-NXT1 RNA-binding activity.<ref>PMID:10786854</ref> <ref>PMID:11158589</ref> <ref>PMID:18364396</ref> [[http://www.uniprot.org/uniprot/ICP27_SHV21 ICP27_SHV21]] Early protein that promotes the accumulation and nuclear export of viral intronless RNA transcripts by interacting with mRNAs and cellular export proteins. Probably acts as a viral splicing factor that regulates viral RNA splicing. Functions as a multifunctional regulator of the expression of viral lytic genes (By similarity). | + | [https://www.uniprot.org/uniprot/ALRF2_MOUSE ALRF2_MOUSE] Export adapter involved in spliced and unspliced mRNA nuclear export. Binds mRNA which is transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway); enhances NXF1-NXT1 RNA-binding activity.<ref>PMID:10786854</ref> <ref>PMID:11158589</ref> <ref>PMID:18364396</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2yka" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Herpesvirus saimiri]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Golovanov, A P]] | + | [[Category: Saimiriine gammaherpesvirus 2]] |
| - | [[Category: Hautbergue, G M]] | + | [[Category: Golovanov AP]] |
| - | [[Category: Kalra, P]] | + | [[Category: Hautbergue GM]] |
| - | [[Category: Tunnicliffe, R B]] | + | [[Category: Kalra P]] |
| - | [[Category: Wilson, S A]] | + | [[Category: Tunnicliffe RB]] |
| - | [[Category: Rna binding protein]] | + | [[Category: Wilson SA]] |
| - | [[Category: Rna binding protein-transcription complex]]
| + | |
| Structural highlights
Function
ALRF2_MOUSE Export adapter involved in spliced and unspliced mRNA nuclear export. Binds mRNA which is transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway); enhances NXF1-NXT1 RNA-binding activity.[1] [2] [3]
Publication Abstract from PubMed
The essential herpesvirus adaptor protein HVS ORF57, which has homologs in all other herpesviruses, promotes viral mRNA export by utilizing the cellular mRNA export machinery. ORF57 protein specifically recognizes viral mRNA transcripts, and binds to proteins of the cellular transcription-export (TREX) complex, in particular ALYREF. This interaction introduces viral mRNA to the NXF1 pathway, subsequently directing it to the nuclear pore for export to the cytoplasm. Here we have used a range of techniques to reveal the sites for direct contact between RNA and ORF57 in the absence and presence of ALYREF. A binding site within ORF57 was characterized which recognizes specific viral mRNA motifs. When ALYREF is present, part of this ORF57 RNA binding site, composed of an alpha-helix, binds preferentially to ALYREF. This competitively displaces viral RNA from the alpha-helix, but contact with RNA is still maintained by a flanking region. At the same time, the flexible N-terminal domain of ALYREF comes into contact with the viral RNA, which becomes engaged in an extensive network of synergistic interactions with both ALYREF and ORF57. Transfer of RNA to ALYREF in the ternary complex, and involvement of individual ORF57 residues in RNA recognition, were confirmed by UV cross-linking and mutagenesis. The atomic-resolution structure of the ORF57-ALYREF interface was determined, which noticeably differed from the homologous ICP27-ALYREF structure. Together, the data provides the first site-specific description of how viral mRNA is locked by a herpes viral adaptor protein in complex with cellular ALYREF, giving herpesvirus access to the cellular mRNA export machinery. The NMR strategy used may be more generally applicable to the study of fuzzy protein-protein-RNA complexes which involve flexible polypeptide regions.
Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF.,Tunnicliffe RB, Hautbergue GM, Wilson SA, Kalra P, Golovanov AP PLoS Pathog. 2014 Feb 13;10(2):e1003907. doi: 10.1371/journal.ppat.1003907., eCollection 2014 Feb. PMID:24550725[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stutz F, Bachi A, Doerks T, Braun IC, Seraphin B, Wilm M, Bork P, Izaurralde E. REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA. 2000 Apr;6(4):638-50. PMID:10786854
- ↑ Rodrigues JP, Rode M, Gatfield D, Blencowe BJ, Carmo-Fonseca M, Izaurralde E. REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1030-5. Epub 2001 Jan 23. PMID:11158589 doi:http://dx.doi.org/10.1073/pnas.031586198
- ↑ Hautbergue GM, Hung ML, Golovanov AP, Lian LY, Wilson SA. Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5154-9. doi:, 10.1073/pnas.0709167105. Epub 2008 Mar 25. PMID:18364396 doi:http://dx.doi.org/10.1073/pnas.0709167105
- ↑ Tunnicliffe RB, Hautbergue GM, Wilson SA, Kalra P, Golovanov AP. Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF. PLoS Pathog. 2014 Feb 13;10(2):e1003907. doi: 10.1371/journal.ppat.1003907., eCollection 2014 Feb. PMID:24550725 doi:http://dx.doi.org/10.1371/journal.ppat.1003907
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