4c0q: Difference between revisions

Latest revision as of 12:01, 20 December 2023

Transportin 3 in complex with Ran(Q69L)GTP

Structural highlights

4c0q is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.42Å
Ligands:	GTP, MG, MSE
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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:https://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:https://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:https://dx.doi.org/10.1073/pnas.1320755111

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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:https://dx.doi.org/10.1073/pnas.181354098

[4] 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:https://dx.doi.org/10.1093/emboj/cdg126

[5] 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:https://dx.doi.org/10.1073/pnas.1320755111

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[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 <StructureSection load='4c0q' size='340' side='right'caption='[[4c0q]], [[Resolution|resolution]] 3.42&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4c0q]] 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=4C0Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C0Q FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4c0q]] 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=4C0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C0Q FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.42&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c0o|4c0o]], [[4c0p|4c0p]]</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=4c0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0q OCA], [https://pdbe.org/4c0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c0q RCSB], [https://www.ebi.ac.uk/pdbsum/4c0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c0q ProSAT]</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=4c0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c0q OCA], [http://pdbe.org/4c0q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c0q RCSB], [http://www.ebi.ac.uk/pdbsum/4c0q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c0q ProSAT]</span></td></tr>
 </table>
 == 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 ==
-[[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>  [[http://www.uniprot.org/uniprot/RAN_HUMAN RAN_HUMAN]] GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</ref>   Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.<ref>PMID:10400640</ref> <ref>PMID:8692944</ref> <ref>PMID:18591255</ref> <ref>PMID:18617507</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;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 ==See Also==
-*[[GTP-binding protein|GTP-binding protein]]
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
-*[[Importin|Importin]]
+*[[Importin 3D structures|Importin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Cherepanov, P]]
+[[Category: Cherepanov P]]
-[[Category: Hare, S]]
+[[Category: Hare S]]
-[[Category: Maertens, G]]
+[[Category: Maertens G]]
-[[Category: Heat repeat]]
-[[Category: Importin beta]]
-[[Category: Nuclear import]]
-[[Category: Transport protein-gtp-binding protein complex]]

4c0q: Difference between revisions

Latest revision as of 12:01, 20 December 2023

Transportin 3 in complex with Ran(Q69L)GTP

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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