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- | [[Image:3gj4.png|left|200px]] | |
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- | <!-- | + | ==Crystal structure of human RanGDP-Nup153ZnF3 complex== |
- | The line below this paragraph, containing "STRUCTURE_3gj4", creates the "Structure Box" on the page.
| + | <StructureSection load='3gj4' size='340' side='right'caption='[[3gj4]], [[Resolution|resolution]] 2.15Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3gj4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GJ4 FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | {{STRUCTURE_3gj4| PDB=3gj4 | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gj4 OCA], [https://pdbe.org/3gj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gj4 RCSB], [https://www.ebi.ac.uk/pdbsum/3gj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gj4 ProSAT]</span></td></tr> |
| + | </table> |
| + | == Function == |
| + | [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> |
| + | == Evolutionary Conservation == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gj/3gj4_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gj4 ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | The nuclear pore complex (NPC) resides in circular openings within the nuclear envelope and serves as the sole conduit to facilitate nucleocytoplasmic transport in eukaryotes. The asymmetric distribution of the small G protein Ran across the nuclear envelope regulates directionality of protein transport. Ran interacts with the NPC of metazoa via two asymmetrically localized components, Nup153 at the nuclear face and Nup358 at the cytoplasmic face. Both nucleoporins contain a stretch of distinct, Ran-binding zinc finger domains. Here, we present six crystal structures of Nup153-zinc fingers in complex with Ran and a 1.48 A crystal structure of RanGDP. Crystal engineering allowed us to obtain well diffracting crystals so that all ZnF-Ran complex structures are refined to high resolution. Each of the four zinc finger modules of Nup153 binds one Ran molecule in apparently non-allosteric fashion. The affinity is measurably higher for RanGDP than for RanGTP and varies modestly between the individual zinc fingers. By microcalorimetric and mutational analysis, we determined that one specific hydrogen bond accounts for most of the differences in the binding affinity of individual zinc fingers. Genomic analysis reveals that only in animals do NPCs contain Ran-binding zinc fingers. We speculate that these organisms evolved a mechanism to maintain a high local concentration of Ran at the vicinity of the NPC, using this zinc finger domain as a sink. |
| | | |
- | ===Crystal structure of human RanGDP-Nup153ZnF3 complex===
| + | Crystallographic and biochemical analysis of the Ran-binding zinc finger domain.,Partridge JR, Schwartz TU J Mol Biol. 2009 Aug 14;391(2):375-89. Epub 2009 Jun 6. PMID:19505478<ref>PMID:19505478</ref> |
| | | |
- | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
- | <!--
| + | </div> |
- | The line below this paragraph, {{ABSTRACT_PUBMED_19505478}}, adds the Publication Abstract to the page
| + | <div class="pdbe-citations 3gj4" style="background-color:#fffaf0;"></div> |
- | (as it appears on PubMed at http://www.pubmed.gov), where 19505478 is the PubMed ID number.
| + | |
- | -->
| + | |
- | {{ABSTRACT_PUBMED_19505478}}
| + | |
- | | + | |
- | ==About this Structure== | + | |
- | [[3gj4]] is a 4 chain structure of [[Nucleoporin]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GJ4 OCA].
| + | |
| | | |
| ==See Also== | | ==See Also== |
- | *[[Nucleoporin]] | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
- | | + | *[[Nucleoporin 3D structures|Nucleoporin 3D structures]] |
- | ==Reference== | + | == References == |
- | <ref group="xtra">PMID:19505478</ref><references group="xtra"/> | + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| + | [[Category: Large Structures]] |
| [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
- | [[Category: Partridge, J R.]] | + | [[Category: Partridge JR]] |
- | [[Category: Schwartz, T U.]] | + | [[Category: Schwartz TU]] |
- | [[Category: Acetylation]]
| + | |
- | [[Category: Cytoplasm]]
| + | |
- | [[Category: Dna-binding]]
| + | |
- | [[Category: G protein]]
| + | |
- | [[Category: Gdp]]
| + | |
- | [[Category: Gtp-binding]]
| + | |
- | [[Category: Host-virus interaction]]
| + | |
- | [[Category: Isopeptide bond]]
| + | |
- | [[Category: Metal-binding]]
| + | |
- | [[Category: Mrna transport]]
| + | |
- | [[Category: Nuclear pore]]
| + | |
- | [[Category: Nuclear pore complex]]
| + | |
- | [[Category: Nucleotide-binding]]
| + | |
- | [[Category: Nucleus]]
| + | |
- | [[Category: Nup153]]
| + | |
- | [[Category: Phosphoprotein]]
| + | |
- | [[Category: Polymorphism]]
| + | |
- | [[Category: Protein transport]]
| + | |
- | [[Category: Ran]]
| + | |
- | [[Category: Translocation]]
| + | |
- | [[Category: Transport]]
| + | |
- | [[Category: Transport protein]]
| + | |
- | [[Category: Ubl conjugation]]
| + | |
- | [[Category: Zinc]]
| + | |
- | [[Category: Zinc finger]]
| + | |
- | [[Category: Zinc-finger]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The nuclear pore complex (NPC) resides in circular openings within the nuclear envelope and serves as the sole conduit to facilitate nucleocytoplasmic transport in eukaryotes. The asymmetric distribution of the small G protein Ran across the nuclear envelope regulates directionality of protein transport. Ran interacts with the NPC of metazoa via two asymmetrically localized components, Nup153 at the nuclear face and Nup358 at the cytoplasmic face. Both nucleoporins contain a stretch of distinct, Ran-binding zinc finger domains. Here, we present six crystal structures of Nup153-zinc fingers in complex with Ran and a 1.48 A crystal structure of RanGDP. Crystal engineering allowed us to obtain well diffracting crystals so that all ZnF-Ran complex structures are refined to high resolution. Each of the four zinc finger modules of Nup153 binds one Ran molecule in apparently non-allosteric fashion. The affinity is measurably higher for RanGDP than for RanGTP and varies modestly between the individual zinc fingers. By microcalorimetric and mutational analysis, we determined that one specific hydrogen bond accounts for most of the differences in the binding affinity of individual zinc fingers. Genomic analysis reveals that only in animals do NPCs contain Ran-binding zinc fingers. We speculate that these organisms evolved a mechanism to maintain a high local concentration of Ran at the vicinity of the NPC, using this zinc finger domain as a sink.
Crystallographic and biochemical analysis of the Ran-binding zinc finger domain.,Partridge JR, Schwartz TU J Mol Biol. 2009 Aug 14;391(2):375-89. Epub 2009 Jun 6. PMID:19505478[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Partridge JR, Schwartz TU. Crystallographic and biochemical analysis of the Ran-binding zinc finger domain. J Mol Biol. 2009 Aug 14;391(2):375-89. Epub 2009 Jun 6. PMID:19505478 doi:10.1016/j.jmb.2009.06.011
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