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[[ | ==Crystal structure of human HDAC6 in complex with ubiquitin== | ||
<StructureSection load='3phd' size='340' side='right' caption='[[3phd]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3phd]] is a 8 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=3PHD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PHD 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> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c5k|3c5k]], [[3gv4|3gv4]], [[2znv|2znv]], [[3nhe|3nhe]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HDAC6, KIAA0901, JM21 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), UBB, UBA52, UBCEP2, UBC, RPS27A, UBA80, UBCEP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </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=3phd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3phd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3phd RCSB], [http://www.ebi.ac.uk/pdbsum/3phd PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The aggresome pathway is activated when proteasomal clearance of misfolded proteins is hindered. Misfolded polyubiquitinated protein aggregates are recruited and transported to the aggresome via the microtubule network by a protein complex consisting of histone deacetylase 6 (HDAC6) and the dynein motor complex. Current model suggests that HDAC6 recognizes protein aggregates by binding directly to polyubiquitinated proteins. Here, we show that there are substantial amounts of unanchored ubiquitin in protein aggregates with solvent accessible C-termini. The ubiquitin binding domain (ZnF-UBP) of HDAC6 binds exclusively to the unanchored C-terminal diglycine motif of ubiquitin instead of conjugated polyubiquitin. The unanchored ubiquitin C-termini in the aggregates are generated in situ by aggregate-associated deubiquitinase ataxin-3. These results provide structural and mechanistic bases for the role of HDAC6 in aggresome formation and further suggest a novel ubiquitin-mediated signaling pathway, where the exposure of ubiquitin C-termini within protein aggregates enables HDAC6 recognition and transport to the aggresome. | |||
Protein aggregates are recruited to the aggresome by histone deacetylase 6 via unanchored ubiquitin C-termini.,Ouyang H, Ali YO, Ravichandran M, Dong A, Qiu W, Mackenzie F, Dhe-Paganon S, Arrowsmith CH, Zhai RG J Biol Chem. 2011 Nov 8. PMID:22069321<ref>PMID:22069321</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Histone deacetylase|Histone deacetylase]] | *[[Histone deacetylase|Histone deacetylase]] | ||
*[[Ubiquitin|Ubiquitin]] | *[[Ubiquitin|Ubiquitin]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Histone deacetylase]] | [[Category: Histone deacetylase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Dong, A | [[Category: Dong, A]] | ||
[[Category: Kozieradzki, I | [[Category: Kozieradzki, I]] | ||
[[Category: Li, F | [[Category: Li, F]] | ||
[[Category: Loppnau, P | [[Category: Loppnau, P]] | ||
[[Category: Mackenzie, F | [[Category: Mackenzie, F]] | ||
[[Category: Ouyang, H | [[Category: Ouyang, H]] | ||
[[Category: Qui, W | [[Category: Qui, W]] | ||
[[Category: Ravichandran, M | [[Category: Ravichandran, M]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: Schuetz, A | [[Category: Schuetz, A]] | ||
[[Category: Hdac6]] | [[Category: Hdac6]] | ||
[[Category: Protein binding]] | [[Category: Protein binding]] | ||
[[Category: Sgc]] | [[Category: Sgc]] | ||
[[Category: Ubiquitin]] | [[Category: Ubiquitin]] | ||
Revision as of 14:57, 9 December 2014
Crystal structure of human HDAC6 in complex with ubiquitinCrystal structure of human HDAC6 in complex with ubiquitin
Structural highlights
Publication Abstract from PubMedThe aggresome pathway is activated when proteasomal clearance of misfolded proteins is hindered. Misfolded polyubiquitinated protein aggregates are recruited and transported to the aggresome via the microtubule network by a protein complex consisting of histone deacetylase 6 (HDAC6) and the dynein motor complex. Current model suggests that HDAC6 recognizes protein aggregates by binding directly to polyubiquitinated proteins. Here, we show that there are substantial amounts of unanchored ubiquitin in protein aggregates with solvent accessible C-termini. The ubiquitin binding domain (ZnF-UBP) of HDAC6 binds exclusively to the unanchored C-terminal diglycine motif of ubiquitin instead of conjugated polyubiquitin. The unanchored ubiquitin C-termini in the aggregates are generated in situ by aggregate-associated deubiquitinase ataxin-3. These results provide structural and mechanistic bases for the role of HDAC6 in aggresome formation and further suggest a novel ubiquitin-mediated signaling pathway, where the exposure of ubiquitin C-termini within protein aggregates enables HDAC6 recognition and transport to the aggresome. Protein aggregates are recruited to the aggresome by histone deacetylase 6 via unanchored ubiquitin C-termini.,Ouyang H, Ali YO, Ravichandran M, Dong A, Qiu W, Mackenzie F, Dhe-Paganon S, Arrowsmith CH, Zhai RG J Biol Chem. 2011 Nov 8. PMID:22069321[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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