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| ==Ubiquitin Recognition by Npl4 Zinc-Fingers== | | ==Ubiquitin Recognition by Npl4 Zinc-Fingers== |
- | <StructureSection load='1q5w' size='340' side='right' caption='[[1q5w]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1q5w' size='340' side='right'caption='[[1q5w]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[1q5w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Q5W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1q5w]] is a 2 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 experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q5W FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nj3|1nj3]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NPL4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), (UBA52 OR UBCEP2) AND UBB AND UBC AND (UBA80 OR UBCEP1 OR RPS27A) ([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=1q5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q5w OCA], [https://pdbe.org/1q5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q5w RCSB], [https://www.ebi.ac.uk/pdbsum/1q5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q5w 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=1q5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q5w OCA], [http://pdbe.org/1q5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q5w RCSB], [http://www.ebi.ac.uk/pdbsum/1q5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q5w ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/NPL4_RAT NPL4_RAT]] The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope.<ref>PMID:10811609</ref> <ref>PMID:11781570</ref> <ref>PMID:11740563</ref> <ref>PMID:14636562</ref> <ref>PMID:12411482</ref> <ref>PMID:12644454</ref> | + | [https://www.uniprot.org/uniprot/NPL4_RAT NPL4_RAT] The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope.<ref>PMID:10811609</ref> <ref>PMID:11781570</ref> <ref>PMID:11740563</ref> <ref>PMID:14636562</ref> <ref>PMID:12411482</ref> <ref>PMID:12644454</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </div> | | </div> |
| <div class="pdbe-citations 1q5w" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1q5w" style="background-color:#fffaf0;"></div> |
| + | |
| + | ==See Also== |
| + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Buffalo rat]] | + | [[Category: Homo sapiens]] |
- | [[Category: Human]] | + | [[Category: Large Structures]] |
- | [[Category: Alam, S L]] | + | [[Category: Rattus norvegicus]] |
- | [[Category: Blake, B K]] | + | [[Category: Alam SL]] |
- | [[Category: Davis, D R]] | + | [[Category: Blake BK]] |
- | [[Category: Emr, S D]] | + | [[Category: Davis DR]] |
- | [[Category: Meyer, H H]] | + | [[Category: Emr SD]] |
- | [[Category: Payne, M]] | + | [[Category: Meyer HH]] |
- | [[Category: Sun, J]] | + | [[Category: Payne M]] |
- | [[Category: Sundquist, W I]] | + | [[Category: Sun J]] |
- | [[Category: Welch, B D]] | + | [[Category: Sundquist WI]] |
- | [[Category: Nzf domain]]
| + | [[Category: Welch BD]] |
- | [[Category: Protein binding]]
| + | |
- | [[Category: Protein-protein complex]]
| + | |
- | [[Category: Rubredoxin knuckle]]
| + | |
- | [[Category: Ubiquitin]]
| + | |
- | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
NPL4_RAT The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope.[1] [2] [3] [4] [5] [6]
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
Ubiquitin (Ub) functions in many different biological pathways, where it typically interacts with proteins that contain modular Ub recognition domains. One such recognition domain is the Npl4 zinc finger (NZF), a compact zinc-binding module found in many proteins that function in Ub-dependent processes. We now report the solution structure of the NZF domain from Npl4 in complex with Ub. The structure reveals that three key NZF residues (13TF14/M25) surrounding the zinc coordination site bind the hydrophobic 'Ile44' surface of Ub. Mutations in the 13TF14/M25 motif inhibit Ub binding, and naturally occurring NZF domains that lack the motif do not bind Ub. However, substitution of the 13TF14/M25 motif into the nonbinding NZF domain from RanBP2 creates Ub-binding activity, demonstrating the versatility of the NZF scaffold. Finally, NZF mutations that inhibit Ub binding by the NZF domain of Vps36/ESCRT-II also inhibit sorting of ubiquitylated proteins into the yeast vacuole. Thus, the NZF is a versatile protein recognition domain that is used to bind ubiquitylated proteins during vacuolar protein sorting, and probably many other biological processes.
Ubiquitin interactions of NZF zinc fingers.,Alam SL, Sun J, Payne M, Welch BD, Blake BK, Davis DR, Meyer HH, Emr SD, Sundquist WI EMBO J. 2004 Apr 7;23(7):1411-21. Epub 2004 Mar 18. PMID:15029239[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Meyer HH, Shorter JG, Seemann J, Pappin D, Warren G. A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways. EMBO J. 2000 May 15;19(10):2181-92. PMID:10811609 doi:http://dx.doi.org/10.1093/emboj/19.10.2181
- ↑ Hetzer M, Meyer HH, Walther TC, Bilbao-Cortes D, Warren G, Mattaj IW. Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly. Nat Cell Biol. 2001 Dec;3(12):1086-91. PMID:11781570 doi:http://dx.doi.org/10.1038/ncb1201-1086
- ↑ Ye Y, Meyer HH, Rapoport TA. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature. 2001 Dec 6;414(6864):652-6. PMID:11740563 doi:http://dx.doi.org/10.1038/414652a
- ↑ Cao K, Nakajima R, Meyer HH, Zheng Y. The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis. Cell. 2003 Oct 31;115(3):355-67. PMID:14636562
- ↑ Meyer HH, Wang Y, Warren G. Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1-Npl4. EMBO J. 2002 Nov 1;21(21):5645-52. PMID:12411482
- ↑ Wang B, Alam SL, Meyer HH, Payne M, Stemmler TL, Davis DR, Sundquist WI. Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4. J Biol Chem. 2003 May 30;278(22):20225-34. Epub 2003 Mar 18. PMID:12644454 doi:10.1074/jbc.M300459200
- ↑ Alam SL, Sun J, Payne M, Welch BD, Blake BK, Davis DR, Meyer HH, Emr SD, Sundquist WI. Ubiquitin interactions of NZF zinc fingers. EMBO J. 2004 Apr 7;23(7):1411-21. Epub 2004 Mar 18. PMID:15029239 doi:10.1038/sj.emboj.7600114
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