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| <StructureSection load='5uwp' size='340' side='right'caption='[[5uwp]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='5uwp' size='340' side='right'caption='[[5uwp]], [[Resolution|resolution]] 2.05Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[5uwp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UWP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UWP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uwp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UWP FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.054Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uwi|5uwi]], [[5uwh|5uwh]], [[5uwj|5uwj]], [[5uwu|5uwu]], [[5uwo|5uwo]], [[5uwq|5uwq]], [[5uwr|5uwr]], [[5uws|5uws]], [[5uwt|5uwt]], [[5uww|5uww]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">RAN, ARA24, OK/SW-cl.81 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), YRB1, CST20, HTN1, SFO1, YDR002W, YD8119.08 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), CRM1, KAP124, XPO1, YGR218W, G8514 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), DIAPH3 ([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=5uwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uwp OCA], [https://pdbe.org/5uwp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uwp RCSB], [https://www.ebi.ac.uk/pdbsum/5uwp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uwp 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=5uwp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uwp OCA], [http://pdbe.org/5uwp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uwp RCSB], [http://www.ebi.ac.uk/pdbsum/5uwp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uwp ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[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> [[http://www.uniprot.org/uniprot/XPO1_YEAST XPO1_YEAST]] Receptor for the leucine-rich nuclear export signal (NES). [[http://www.uniprot.org/uniprot/YRB1_YEAST YRB1_YEAST]] Important for the export of protein containing nuclear export signal (NES) out of the nucleus. Stimulates the GTPase activity of GSP1 and GSP2. | + | [https://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> |
- | <div style="background-color:#fffaf0;">
| + | |
- | == Publication Abstract from PubMed ==
| + | |
- | Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.
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- | | + | |
- | Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals.,Fung HY, Fu SC, Chook YM Elife. 2017 Mar 10;6. pii: e23961. doi: 10.7554/eLife.23961. PMID:28282025<ref>PMID:28282025</ref>
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- | | + | |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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- | </div>
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- | <div class="pdbe-citations 5uwp" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Atcc 18824]] | + | [[Category: Homo sapiens]] |
- | [[Category: Human]]
| + | |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Chook, Y M]] | + | [[Category: Saccharomyces cerevisiae]] |
- | [[Category: Fung, H Y.J]] | + | [[Category: Chook YM]] |
- | [[Category: Heat repeat]] | + | [[Category: Fung HYJ]] |
- | [[Category: Karyopherin]]
| + | |
- | [[Category: Ne]]
| + | |
- | [[Category: Nuclear export]]
| + | |
- | [[Category: Protein transport]]
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| Structural highlights
Function
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.[1] [2] [3] [4] Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases.[5] [6] [7] [8]
See Also
References
- ↑ 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
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