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| | ==Unliganded Transportin 3== | | ==Unliganded Transportin 3== |
| - | <StructureSection load='4c0p' size='340' side='right' caption='[[4c0p]], [[Resolution|resolution]] 2.95Å' scene=''> | + | <StructureSection load='4c0p' size='340' side='right'caption='[[4c0p]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c0p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C0P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c0p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C0P FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c0o|4c0o]], [[4c0q|4c0q]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4c0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c0p RCSB], [http://www.ebi.ac.uk/pdbsum/4c0p 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=4c0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0p OCA], [https://pdbe.org/4c0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c0p RCSB], [https://www.ebi.ac.uk/pdbsum/4c0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c0p ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN]] Primary biliary cirrhosis;Autosomal dominant limb-girdle muscular dystrophy type 1F. | + | [https://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN] Primary biliary cirrhosis;Autosomal dominant limb-girdle muscular dystrophy type 1F. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN]] Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins RBM4, SFRS1 and SFRS2, by recognizing phosphorylated RS domains.<ref>PMID:10366588</ref> <ref>PMID:10713112</ref> <ref>PMID:11517331</ref> <ref>PMID:12628928</ref> | + | [https://www.uniprot.org/uniprot/TNPO3_HUMAN TNPO3_HUMAN] Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins RBM4, SFRS1 and SFRS2, by recognizing phosphorylated RS domains.<ref>PMID:10366588</ref> <ref>PMID:10713112</ref> <ref>PMID:11517331</ref> <ref>PMID:12628928</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | Structural basis for nuclear import of splicing factors by human Transportin 3.,Maertens GN, Cook NJ, Wang W, Hare S, Gupta SS, Oztop I, Lee K, Pye VE, Cosnefroy O, Snijders AP, Kewalramani VN, Fassati A, Engelman A, Cherepanov P Proc Natl Acad Sci U S A. 2014 Jan 21. PMID:24449914<ref>PMID:24449914</ref> | | Structural basis for nuclear import of splicing factors by human Transportin 3.,Maertens GN, Cook NJ, Wang W, Hare S, Gupta SS, Oztop I, Lee K, Pye VE, Cosnefroy O, Snijders AP, Kewalramani VN, Fassati A, Engelman A, Cherepanov P Proc Natl Acad Sci U S A. 2014 Jan 21. PMID:24449914<ref>PMID:24449914</ref> |
| | | | |
| - | 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 4c0p" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Importin 3D structures|Importin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cherepanov, P.]] | + | [[Category: Large Structures]] |
| - | [[Category: Cook, N J.]] | + | [[Category: Cherepanov P]] |
| - | [[Category: Hare, S.]] | + | [[Category: Cook NJ]] |
| - | [[Category: Maertens, G N.]] | + | [[Category: Hare S]] |
| - | [[Category: Heat repeat]] | + | [[Category: Maertens GN]] |
| - | [[Category: Nuclear import]]
| + | |
| - | [[Category: Tnpo3]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Disease
TNPO3_HUMAN Primary biliary cirrhosis;Autosomal dominant limb-girdle muscular dystrophy type 1F.
Function
TNPO3_HUMAN Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins RBM4, SFRS1 and SFRS2, by recognizing phosphorylated RS domains.[1] [2] [3] [4]
Publication Abstract from PubMed
Transportin 3 (Tnpo3, Transportin-SR2) is implicated in nuclear import of splicing factors and HIV-1 replication. Herein, we show that the majority of cellular Tnpo3 binding partners contain arginine-serine (RS) repeat domains and present crystal structures of human Tnpo3 in its free as well as GTPase Ran- and alternative splicing factor/splicing factor 2 (ASF/SF2)-bound forms. The flexible beta-karyopherin fold of Tnpo3 embraces the RNA recognition motif and RS domains of the cargo. A constellation of charged residues on and around the arginine-rich helix of Tnpo3 HEAT repeat 15 engage the phosphorylated RS domain and are critical for the recognition and nuclear import of ASF/SF2. Mutations in the same region of Tnpo3 impair its interaction with the cleavage and polyadenylation specificity factor 6 (CPSF6) and its ability to support HIV-1 replication. Steric incompatibility of the RS domain and RanGTP engagement by Tnpo3 provides the mechanism for cargo release in the nucleus. Our results elucidate the structural bases for nuclear import of splicing factors and the Tnpo3-CPSF6 nexus in HIV-1 biology.
Structural basis for nuclear import of splicing factors by human Transportin 3.,Maertens GN, Cook NJ, Wang W, Hare S, Gupta SS, Oztop I, Lee K, Pye VE, Cosnefroy O, Snijders AP, Kewalramani VN, Fassati A, Engelman A, Cherepanov P Proc Natl Acad Sci U S A. 2014 Jan 21. PMID:24449914[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kataoka N, Bachorik JL, Dreyfuss G. Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol. 1999 Jun 14;145(6):1145-52. PMID:10366588
- ↑ Lai MC, Lin RI, Huang SY, Tsai CW, Tarn WY. A human importin-beta family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J Biol Chem. 2000 Mar 17;275(11):7950-7. PMID:10713112
- ↑ Lai MC, Lin RI, Tarn WY. Transportin-SR2 mediates nuclear import of phosphorylated SR proteins. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10154-9. Epub 2001 Aug 21. PMID:11517331 doi:http://dx.doi.org/10.1073/pnas.181354098
- ↑ Lai MC, Kuo HW, Chang WC, Tarn WY. A novel splicing regulator shares a nuclear import pathway with SR proteins. EMBO J. 2003 Mar 17;22(6):1359-69. PMID:12628928 doi:http://dx.doi.org/10.1093/emboj/cdg126
- ↑ Maertens GN, Cook NJ, Wang W, Hare S, Gupta SS, Oztop I, Lee K, Pye VE, Cosnefroy O, Snijders AP, Kewalramani VN, Fassati A, Engelman A, Cherepanov P. Structural basis for nuclear import of splicing factors by human Transportin 3. Proc Natl Acad Sci U S A. 2014 Jan 21. PMID:24449914 doi:http://dx.doi.org/10.1073/pnas.1320755111
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