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| | <StructureSection load='2kt5' size='340' side='right' caption='[[2kt5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | | <StructureSection load='2kt5' size='340' side='right' caption='[[2kt5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kt5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_1 Human herpesvirus 1] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KT5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KT5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kt5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-1 Hhv-1] 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=2KT5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KT5 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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f3j|2f3j]]</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Refbp2, Ref2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Refbp2, Ref2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2kt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kt5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kt5 RCSB], [http://www.ebi.ac.uk/pdbsum/2kt5 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=2kt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kt5 OCA], [http://pdbe.org/2kt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kt5 RCSB], [http://www.ebi.ac.uk/pdbsum/2kt5 PDBsum]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/REFP2_MOUSE REFP2_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/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 2kt5" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human herpesvirus 1]] | + | [[Category: Hhv-1]] |
| - | [[Category: Mus musculus]] | + | [[Category: Lk3 transgenic mice]] |
| | [[Category: Golovanov, A P]] | | [[Category: Golovanov, A P]] |
| | [[Category: Hautbergue, G M]] | | [[Category: Hautbergue, G M]] |
| 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 herpesvirus proteins HSV-1 ICP27 and HVS ORF57 promote viral mRNA export by utilizing the cellular mRNA export machinery. This function is triggered by binding to proteins of the transcription-export (TREX) complex, in particular to REF/Aly which directs viral mRNA to the TAP/NFX1 pathway and, subsequently, to the nuclear pore for export to the cytoplasm. Here we have determined the structure of the REF-ICP27 interaction interface at atomic-resolution and provided a detailed comparison of the binding interfaces between ICP27, ORF57 and REF using solution-state NMR. Despite the absence of any obvious sequence similarity, both viral proteins bind on the same site of the folded RRM domain of REF, via short but specific recognition sites. The regions of ICP27 and ORF57 involved in binding by REF have been mapped as residues 104-112 and 103-120, respectively. We have identified the pattern of residues critical for REF/Aly recognition, common to both ICP27 and ORF57. The importance of the key amino acid residues within these binding sites was confirmed by site-directed mutagenesis. The functional significance of the ORF57-REF/Aly interaction was also probed using an ex vivo cytoplasmic viral mRNA accumulation assay and this revealed that mutants that reduce the protein-protein interaction dramatically decrease the ability of ORF57 to mediate the nuclear export of intronless viral mRNA. Together these data precisely map amino acid residues responsible for the direct interactions between viral adaptors and cellular REF/Aly and provide the first molecular details of how herpes viruses access the cellular mRNA export pathway.
Structural Basis for the Recognition of Cellular mRNA Export Factor REF by Herpes Viral Proteins HSV-1 ICP27 and HVS ORF57.,Tunnicliffe RB, Hautbergue GM, Kalra P, Jackson BR, Whitehouse A, Wilson SA, Golovanov AP PLoS Pathog. 2011 Jan 6;7(1):e1001244. PMID:21253573[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, Kalra P, Jackson BR, Whitehouse A, Wilson SA, Golovanov AP. Structural Basis for the Recognition of Cellular mRNA Export Factor REF by Herpes Viral Proteins HSV-1 ICP27 and HVS ORF57. PLoS Pathog. 2011 Jan 6;7(1):e1001244. PMID:21253573 doi:10.1371/journal.ppat.1001244
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