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| | ==Structure of the N-terminal domain of Nup358== | | ==Structure of the N-terminal domain of Nup358== |
| - | <StructureSection load='4ga0' size='340' side='right' caption='[[4ga0]], [[Resolution|resolution]] 1.15Å' scene=''> | + | <StructureSection load='4ga0' size='340' side='right'caption='[[4ga0]], [[Resolution|resolution]] 1.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ga0]] is a 1 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=4GA0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GA0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ga0]] is a 1 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=4GA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GA0 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ga1|4ga1]], [[4ga2|4ga2]]</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]] 1.15Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RANBP2, NUP358 ([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=4ga0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ga0 OCA], [https://pdbe.org/4ga0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ga0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ga0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ga0 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=4ga0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ga0 OCA], [http://pdbe.org/4ga0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ga0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ga0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ga0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN]] Defects in RANBP2 are the cause of encephalopathy acute infection-induced type 3 (IIAE3) [MIM:[http://omim.org/entry/608033 608033]]. A rapidly progressive encephalopathy manifesting in susceptibile individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. Note=Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815).<ref>PMID:19118815</ref> | + | [https://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN] Defects in RANBP2 are the cause of encephalopathy acute infection-induced type 3 (IIAE3) [MIM:[https://omim.org/entry/608033 608033]. A rapidly progressive encephalopathy manifesting in susceptibile individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. Note=Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815).<ref>PMID:19118815</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN]] E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1.<ref>PMID:11792325</ref> <ref>PMID:12032081</ref> <ref>PMID:15378033</ref> <ref>PMID:15931224</ref> | + | [https://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN] E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1.<ref>PMID:11792325</ref> <ref>PMID:12032081</ref> <ref>PMID:15378033</ref> <ref>PMID:15931224</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Key steps in mRNA export are the nuclear assembly of messenger ribonucleoprotein particles (mRNPs), the translocation of mRNPs through the nuclear pore complex (NPC), and the mRNP remodeling events at the cytoplasmic side of the NPC. Nup358/RanBP2 is a constituent of the cytoplasmic filaments of the NPC specific to higher eukaryotes and provides a multitude of binding sites for the nucleocytoplasmic transport machinery. Here, we present the crystal structure of the Nup358 N-terminal domain (NTD) at 0.95A resolution. The structure reveals an alpha-helical domain that harbors three central tetratricopeptide repeats (TPRs), flanked on each side by an additional solvating amphipathic alpha helix. Overall, the NTD adopts an unusual extended conformation that lacks the characteristic peptide-binding groove observed in canonical TPR domains. Strikingly, the vast majority of the NTD surface exhibits an evolutionarily conserved, positive electrostatic potential, and we demonstrate that the NTD possesses the capability to bind single-stranded RNA in solution. Together, these data suggest that the NTD contributes to mRNP remodeling events at the cytoplasmic face of the NPC.
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| - | | + | |
| - | Crystal Structure of the N-Terminal Domain of Nup358/RanBP2.,Kassube SA, Stuwe T, Lin DH, Antonuk CD, Napetschnig J, Blobel G, Hoelz A J Mol Biol. 2012 Sep 7. pii: S0022-2836(12)00719-X. doi:, 10.1016/j.jmb.2012.08.026. PMID:22959972<ref>PMID:22959972</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4ga0" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hoelz, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Kassube, S A]] | + | [[Category: Hoelz A]] |
| - | [[Category: Lin, D H]] | + | [[Category: Kassube SA]] |
| - | [[Category: Stuwe, T]] | + | [[Category: Lin DH]] |
| - | [[Category: Nuclear pore complex component nucleocytoplasmic transport]] | + | [[Category: Stuwe T]] |
| - | [[Category: Tpr motif]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Disease
RBP2_HUMAN Defects in RANBP2 are the cause of encephalopathy acute infection-induced type 3 (IIAE3) [MIM:608033. A rapidly progressive encephalopathy manifesting in susceptibile individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. Note=Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815).[1]
Function
RBP2_HUMAN E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1.[2] [3] [4] [5]
References
- ↑ Neilson DE, Adams MD, Orr CM, Schelling DK, Eiben RM, Kerr DS, Anderson J, Bassuk AG, Bye AM, Childs AM, Clarke A, Crow YJ, Di Rocco M, Dohna-Schwake C, Dueckers G, Fasano AE, Gika AD, Gionnis D, Gorman MP, Grattan-Smith PJ, Hackenberg A, Kuster A, Lentschig MG, Lopez-Laso E, Marco EJ, Mastroyianni S, Perrier J, Schmitt-Mechelke T, Servidei S, Skardoutsou A, Uldall P, van der Knaap MS, Goglin KC, Tefft DL, Aubin C, de Jager P, Hafler D, Warman ML. Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2. Am J Hum Genet. 2009 Jan;84(1):44-51. doi: 10.1016/j.ajhg.2008.12.009. PMID:19118815 doi:10.1016/j.ajhg.2008.12.009
- ↑ Pichler A, Gast A, Seeler JS, Dejean A, Melchior F. The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell. 2002 Jan 11;108(1):109-20. PMID:11792325
- ↑ Kirsh O, Seeler JS, Pichler A, Gast A, Muller S, Miska E, Mathieu M, Harel-Bellan A, Kouzarides T, Melchior F, Dejean A. The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase. EMBO J. 2002 Jun 3;21(11):2682-91. PMID:12032081 doi:10.1093/emboj/21.11.2682
- ↑ Pichler A, Knipscheer P, Saitoh H, Sixma TK, Melchior F. The RanBP2 SUMO E3 ligase is neither HECT- nor RING-type. Nat Struct Mol Biol. 2004 Oct;11(10):984-91. Epub 2004 Sep 19. PMID:15378033 doi:10.1038/nsmb834
- ↑ Reverter D, Lima CD. Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature. 2005 Jun 2;435(7042):687-92. PMID:15931224 doi:10.1038/nature03588
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