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PDBsum entry 3phd

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protein ligands metals Protein-protein interface(s) links
Protein binding PDB id
3phd
Jmol
Contents
Protein chains
102 a.a. *
85 a.a. *
14 a.a. *
40 a.a. *
39 a.a. *
Ligands
ARG-LEU-ARG-GLY-
GLY
Metals
_ZN ×12
Waters ×2
* Residue conservation analysis
PDB id:
3phd
Name: Protein binding
Title: Crystal structure of human hdac6 in complex with ubiquitin
Structure: Histone deacetylase 6. Chain: a, b, c, d. Synonym: hd6. Engineered: yes. Polyubiquitin. Chain: e, f, g, h. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hdac6, kiaa0901, jm21. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ubb, uba52, ubcep2, ubc, rps27a, uba80, ubcep1. Expression_system_taxid: 562
Resolution:
3.00Å     R-factor:   0.235     R-free:   0.265
Authors: A.Dong,W.Qui,M.Ravichandran,A.Schuetz,P.Loppnau,F.Li,F.Macke I.Kozieradzki,H.Ouyang,Structural Genomics Consortium (Sgc)
Key ref: H.Ouyang et al. (2012). Protein aggregates are recruited to aggresome by histone deacetylase 6 via unanchored ubiquitin C termini. J Biol Chem, 287, 2317-2327. PubMed id: 22069321 DOI: 10.1074/jbc.M111.273730
Date:
03-Nov-10     Release date:   23-Feb-11    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9UBN7  (HDAC6_HUMAN) -  Histone deacetylase 6
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1215 a.a.
102 a.a.
Protein chains
Pfam   ArchSchema ?
Q9UBN7  (HDAC6_HUMAN) -  Histone deacetylase 6
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1215 a.a.
85 a.a.
Protein chain
Pfam   ArchSchema ?
P0CG47  (UBB_HUMAN) -  Polyubiquitin-B
Seq:
Struc:
229 a.a.
14 a.a.*
Protein chain
Pfam   ArchSchema ?
P0CG47  (UBB_HUMAN) -  Polyubiquitin-B
Seq:
Struc:
229 a.a.
40 a.a.*
Protein chain
Pfam   ArchSchema ?
P0CG47  (UBB_HUMAN) -  Polyubiquitin-B
Seq:
Struc:
229 a.a.
39 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.3.5.1.98  - Histone deacetylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     zinc ion binding     1 term  

 

 
DOI no: 10.1074/jbc.M111.273730 J Biol Chem 287:2317-2327 (2012)
PubMed id: 22069321  
 
 
Protein aggregates are recruited to aggresome by histone deacetylase 6 via unanchored ubiquitin C termini.
H.Ouyang, Y.O.Ali, M.Ravichandran, A.Dong, W.Qiu, F.MacKenzie, S.Dhe-Paganon, C.H.Arrowsmith, R.G.Zhai.
 
  ABSTRACT  
 
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. The 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.