3hve

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{{STRUCTURE_3hve| PDB=3hve | SCENE= }}
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==Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases: GigaxoninBTB/3-box==
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===Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases: GigaxoninBTB/3-box===
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<StructureSection load='3hve' size='340' side='right' caption='[[3hve]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19818708}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3hve]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HVE FirstGlance]. <br>
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hqi|3hqi]], [[3hql|3hql]], [[3hqm|3hqm]], [[3htm|3htm]], [[3hu6|3hu6]], [[3hsv|3hsv]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAN, GAN1, KLHL16 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=3hve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hve OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hve RCSB], [http://www.ebi.ac.uk/pdbsum/3hve PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/GAN_HUMAN GAN_HUMAN]] Defects in GAN are the cause of giant axonal neuropathy (GAN) [MIM:[http://omim.org/entry/256850 256850]]. GAN is a severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. It is characterized by neurofilament accumulation, leading to segmental distention of axons.<ref>PMID:16303566</ref> <ref>PMID:11062483</ref> <ref>PMID:11971098</ref> <ref>PMID:12655563</ref> <ref>PMID:17578852</ref> <ref>PMID:17587580</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/GAN_HUMAN GAN_HUMAN]] Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. Substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB. Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival.<ref>PMID:12147674</ref> <ref>PMID:14528312</ref> <ref>PMID:16303566</ref> <ref>PMID:15983046</ref> <ref>PMID:16227972</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hv/3hve_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In the largest E3 ligase subfamily, Cul3 binds a BTB domain, and an associated protein-interaction domain such as MATH recruits substrates for ubiquitination. Here, we present biochemical and structural analyses of the MATH-BTB protein, SPOP. We define a SPOP-binding consensus (SBC) and determine structures revealing recognition of SBCs from the phosphatase Puc, the transcriptional regulator Ci, and the chromatin component MacroH2A. We identify a dimeric SPOP-Cul3 assembly involving a conserved helical structure C-terminal of BTB domains, which we call "3-box" due to its facilitating Cul3 binding and its resemblance to F-/SOCS-boxes in other cullin-based E3s. Structural flexibility between the substrate-binding MATH and Cul3-binding BTB/3-box domains potentially allows a SPOP dimer to engage multiple SBCs found within a single substrate, such as Puc. These studies provide a molecular understanding of how MATH-BTB proteins recruit substrates to Cul3 and how their dimerization and conformational variability may facilitate avid interactions with diverse substrates.
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==Disease==
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Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.,Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA Mol Cell. 2009 Oct 9;36(1):39-50. PMID:19818708<ref>PMID:19818708</ref>
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[[http://www.uniprot.org/uniprot/GAN_HUMAN GAN_HUMAN]] Defects in GAN are the cause of giant axonal neuropathy (GAN) [MIM:[http://omim.org/entry/256850 256850]]. GAN is a severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. It is characterized by neurofilament accumulation, leading to segmental distention of axons.<ref>PMID:16303566</ref><ref>PMID:11062483</ref><ref>PMID:11971098</ref><ref>PMID:12655563</ref><ref>PMID:17578852</ref><ref>PMID:17587580</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/GAN_HUMAN GAN_HUMAN]] Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. Substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB. Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival.<ref>PMID:12147674</ref><ref>PMID:14528312</ref><ref>PMID:16303566</ref><ref>PMID:15983046</ref><ref>PMID:16227972</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[3hve]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HVE OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:019818708</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Schulman, B A.]]
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[[Category: Schulman, B A]]
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[[Category: Zhuang, M.]]
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[[Category: Zhuang, M]]
[[Category: Cytoskeleton]]
[[Category: Cytoskeleton]]
[[Category: Disease mutation]]
[[Category: Disease mutation]]

Revision as of 17:53, 18 December 2014

Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases: GigaxoninBTB/3-box

3hve, resolution 2.80Å

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