5dlq: Difference between revisions

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<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 ==
== Structural highlights ==
<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>
<table><tr><td colspan='2'>[[5dlq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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 [https://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" id="ligandDat"><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]] 3.2&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CT:HYPUSINE'>5CT</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5dlq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlq OCA], [https://pdbe.org/5dlq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dlq RCSB], [https://www.ebi.ac.uk/pdbsum/5dlq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dlq ProSAT]</span></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>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/XPO4_MOUSE 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). [[http://www.uniprot.org/uniprot/IF5A1_HUMAN 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.<ref>PMID:15371445</ref> <ref>PMID:15452064</ref> <ref>PMID:16987817</ref> <ref>PMID:17187778</ref> <ref>PMID:17360499</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/XPO4_MOUSE 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).
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Aksu, M]]
[[Category: Aksu M]]
[[Category: Gorlich, D]]
[[Category: Gorlich D]]
[[Category: Trakhanov, S]]
[[Category: Trakhanov S]]
[[Category: Active transport]]
[[Category: Eif5a]]
[[Category: Exportin]]
[[Category: Gtpase]]
[[Category: Heat repeat]]
[[Category: Hypusine]]
[[Category: Nuclear export importin-beta family]]
[[Category: Nuclear transport]]
[[Category: Nucleotide binding]]
[[Category: Protein transport]]
[[Category: Translation factor]]
[[Category: Unusual amino acid]]

Revision as of 00:48, 29 June 2023

Crystal structure of RanGTP-Exportin 4-eIF5A complexCrystal structure of RanGTP-Exportin 4-eIF5A complex

Structural highlights

5dlq is a 6 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.2Å
Ligands:, ,
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).

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[1]

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

See Also

References

  1. 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

5dlq, resolution 3.20Å

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