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5dlq

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Revision as of 08:09, 8 April 2020

Crystal structure of RanGTP-Exportin 4-eIF5A complex

Structural highlights

5dlq is a 6 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Gene:	Xpo4, Kiaa1721 (LK3 transgenic mice), RAN, ARA24, OK/SW-cl.81 (HUMAN), EIF5A (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[XPO4_MOUSE] Mediates the nuclear export of proteins (cargos) with broad substrate specificity. In the nucleus binds cooperatively to its cargo and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. XPO4 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). [IF5A1_HUMAN] mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis. Regulates also TNF-alpha-mediated apoptosis. Mediates effects of polyamines on neuronal process extension and survival. May play an important role in brain development and function, and in skeletal muscle stem cell differentiation. Also described as a cellular cofactor of human T-cell leukemia virus type I (HTLV-1) Rex protein and of human immunodeficiency virus type 1 (HIV-1) Rev protein, essential for mRNA export of retroviral transcripts.^[1] ^[2] ^[3] ^[4] ^[5] [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.^[6] ^[7] ^[8] ^[9] Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.^[10] ^[11] ^[12] ^[13]

Publication Abstract from PubMed

Xpo4 is a bidirectional nuclear transport receptor that mediates nuclear export of eIF5A and Smad3 as well as import of Sox2 and SRY. How Xpo4 recognizes such a variety of cargoes is as yet unknown. Here we present the crystal structure of the RanGTP.Xpo4.eIF5A export complex at 3.2 A resolution. Xpo4 has a similar structure as CRM1, but the NES-binding site is occluded, and a new interaction site evolved that recognizes both globular domains of eIF5A. eIF5A contains hypusine, a unique amino acid with two positive charges, which is essential for cell viability and eIF5A function in translation. The hypusine docks into a deep, acidic pocket of Xpo4 and is thus a critical element of eIF5A's complex export signature. This further suggests that Xpo4 recognizes other cargoes differently, and illustrates how Xpo4 suppresses - in a chaperone-like manner - undesired interactions of eIF5A inside nuclei.

Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A.,Aksu M, Trakhanov S, Gorlich D Nat Commun. 2016 Jun 16;7:11952. doi: 10.1038/ncomms11952. PMID:27306458^[14]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Li AL, Li HY, Jin BF, Ye QN, Zhou T, Yu XD, Pan X, Man JH, He K, Yu M, Hu MR, Wang J, Yang SC, Shen BF, Zhang XM. A novel eIF5A complex functions as a regulator of p53 and p53-dependent apoptosis. J Biol Chem. 2004 Nov 19;279(47):49251-8. Epub 2004 Sep 14. PMID:15371445 doi:http://dx.doi.org/10.1074/jbc.M407165200
↑ Taylor CA, Senchyna M, Flanagan J, Joyce EM, Cliche DO, Boone AN, Culp-Stewart S, Thompson JE. Role of eIF5A in TNF-alpha-mediated apoptosis of lamina cribrosa cells. Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3568-76. PMID:15452064 doi:http://dx.doi.org/10.1167/iovs.03-1367
↑ Schrader R, Young C, Kozian D, Hoffmann R, Lottspeich F. Temperature-sensitive eIF5A mutant accumulates transcripts targeted to the nonsense-mediated decay pathway. J Biol Chem. 2006 Nov 17;281(46):35336-46. Epub 2006 Sep 20. PMID:16987817 doi:http://dx.doi.org/M601460200
↑ Taylor CA, Sun Z, Cliche DO, Ming H, Eshaque B, Jin S, Hopkins MT, Thai B, Thompson JE. Eukaryotic translation initiation factor 5A induces apoptosis in colon cancer cells and associates with the nucleus in response to tumour necrosis factor alpha signalling. Exp Cell Res. 2007 Feb 1;313(3):437-49. Epub 2006 Oct 28. PMID:17187778 doi:http://dx.doi.org/S0014-4827(06)00389-2
↑ Huang Y, Higginson DS, Hester L, Park MH, Snyder SH. Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4194-9. Epub 2007 Feb 28. PMID:17360499 doi:http://dx.doi.org/0611609104
↑ Hsiao PW, Lin DL, Nakao R, Chang C. The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem. 1999 Jul 16;274(29):20229-34. PMID:10400640
↑ Moroianu J, Blobel G, Radu A. Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7059-62. PMID:8692944
↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
↑ Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008 Nov;7(11):2199-214. doi: 10.1074/mcp.M700586-MCP200., Epub 2008 Jul 9. PMID:18617507 doi:10.1074/mcp.M700586-MCP200
↑ Hsiao PW, Lin DL, Nakao R, Chang C. The linkage of Kennedy's neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem. 1999 Jul 16;274(29):20229-34. PMID:10400640
↑ Moroianu J, Blobel G, Radu A. Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7059-62. PMID:8692944
↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
↑ Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008 Nov;7(11):2199-214. doi: 10.1074/mcp.M700586-MCP200., Epub 2008 Jul 9. PMID:18617507 doi:10.1074/mcp.M700586-MCP200
↑ Aksu M, Trakhanov S, Gorlich D. Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A. Nat Commun. 2016 Jun 16;7:11952. doi: 10.1038/ncomms11952. PMID:27306458 doi:http://dx.doi.org/10.1038/ncomms11952

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5dlq"

@@ Line 1: / Line 1: @@
 ==Crystal structure of RanGTP-Exportin 4-eIF5A complex==
-<StructureSection load='5dlq' size='340' side='right' caption='[[5dlq]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='5dlq' size='340' side='right'caption='[[5dlq]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5dlq]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DLQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DLQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5dlq]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DLQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DLQ 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='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></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CT:HYPUSINE'>5CT</scene></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=5dlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlq OCA], [http://pdbe.org/5dlq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dlq RCSB], [http://www.ebi.ac.uk/pdbsum/5dlq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dlq ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Xpo4, Kiaa1721 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), RAN, ARA24, OK/SW-cl.81 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF5A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlq OCA], [http://pdbe.org/5dlq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dlq RCSB], [http://www.ebi.ac.uk/pdbsum/5dlq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dlq ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5dlq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
+*[[Exportin 3D structures|Exportin 3D structures]]
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Aksu, M]]
 [[Category: Gorlich, D]]

5dlq

From Proteopedia

Revision as of 08:09, 8 April 2020

Crystal structure of RanGTP-Exportin 4-eIF5A complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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