PDBsum entry 2h8n

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protein Protein-protein interface(s) links
Transcription PDB id
Protein chains
68 a.a. *
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Structure of a glutamine-rich domain from histone deacetylase 4
Structure: Histone deacetylase 4. Chain: a, b, c, d. Fragment: n-terminal glutamine-rich domain, residues 62- 129. Synonym: hd4. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hdac4, kiaa0288. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.60Å     R-factor:   0.281     R-free:   0.307
Authors: L.Guo,A.Han,D.L.Bates,L.Chen
Key ref:
L.Guo et al. (2007). Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains. Proc Natl Acad Sci U S A, 104, 4297-4302. PubMed id: 17360518 DOI: 10.1073/pnas.0608041104
07-Jun-06     Release date:   27-Feb-07    
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Protein chains
Pfam   ArchSchema ?
P56524  (HDAC4_HUMAN) -  Histone deacetylase 4
1084 a.a.
68 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Histone deacetylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]


DOI no: 10.1073/pnas.0608041104 Proc Natl Acad Sci U S A 104:4297-4302 (2007)
PubMed id: 17360518  
Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains.
L.Guo, A.Han, D.L.Bates, J.Cao, L.Chen.
Glutamine-rich sequences exist in a wide range of proteins across multiple species. A subset of glutamine-rich sequences has been shown to form amyloid fibers implicated in human diseases. The physiological functions of these sequence motifs are not well understood, partly because of the lack of structural information. Here we have determined a high-resolution structure of a glutamine-rich domain from human histone deacetylase 4 (HDAC4) by x-ray crystallography. The glutamine-rich domain of HDAC4 (19 glutamines of 68 residues) folds into a straight alpha-helix that assembles as a tetramer. In contrast to most coiled coil proteins, the HDAC4 tetramer lacks regularly arranged apolar residues and an extended hydrophobic core. Instead, the protein interfaces consist of multiple hydrophobic patches interspersed with polar interaction networks, wherein clusters of glutamines engage in extensive intra- and interhelical interactions. In solution, the HDAC4 tetramer undergoes rapid equilibrium with monomer and intermediate species. Structure-guided mutations that expand or disrupt hydrophobic patches drive the equilibrium toward the tetramer or monomer, respectively. We propose that a general role of glutamine-rich motifs be to mediate protein-protein interactions characteristic of a large component of polar interaction networks that may facilitate reversible assembly and disassembly of protein complexes.
  Selected figure(s)  
Figure 2.
Fig. 2. Conserved assembly interactions in the HDAC4 tetramer. (a) Schematic presentation of interhelical interactions between monomer A and its neighboring helices B, C, and D. (Top) Interactions between A and C. Residues of A interacting with C are in green, whereas residues in C contacting A are in red. The dotted lines indicate approximately the location of contacts. (Middle) Interactions between A and B. Residues of A interacting with B are in magenta, whereas residues in B contacting A are in red. (Bottom) Interactions between A and D. Residues of A interacting with D are in blue, whereas residues in D contacting A are in red. (b) Sequence alignment of the glutamine-rich motif of class II HDACs from a variety of species (H4, human HDAC4; M4, mouse HDAC4; C4, chicken HDAC4; Z4, zebrafish HDAC4; F4, Drosophila HDAC4; H9, human HDAC9; X9, Xenopus HDAC9; Z9, zebrafish HDAC9; H5, human HDAC5; and M5, mouse HDAC5). Numbering is based on human HDAC4. Colored checks above the sequence denote various modes of interhelical interactions: green, A/C; magenta, A/B; blue, A/D.
Figure 3.
Fig. 3. Protein–protein interactions in the HDAC4 tetramer. (a) The knob-into-hole type of interactions between helix A and C. (b) His-104 of helix C fails to fill in the hole of Leu-78, Lys-81, Gln-82, and Gln-85 of helix A because of the straight helical conformation. A polar interaction network is formed here (see Detailed Protein–Protein Interactions). (c) Interactions between helix A and helix C near the twofold axis. The extrahelical hydrophobic patch formed by Leu-89, Ile-90, and Phe-93 of helix A and C pack against the corresponding region of helix B and D (behind helix A/C, residues not shown, also see SI Fig. 7). (d) A hydration pocket (blue circle) in the HDAC4 tetramer is surrounded by a polar interaction network.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21499245 A.S.Olia, P.E.Prevelige, J.E.Johnson, and G.Cingolani (2011).
Three-dimensional structure of a viral genome-delivery portal vertex.
  Nat Struct Mol Biol, 18, 597-603.
PDB codes: 1vt0 3lj4 3lj5
21183761 S.Wang, J.Du, H.Tang, X.Ding, M.Zha, and Z.Xu (2011).
Expression, purification, crystallization, and preliminary X-ray diffraction analysis of the human TLE1 Q domain.
  Acta Biochim Biophys Sin (Shanghai), 43, 149-153.  
21183075 F.Fiumara, L.Fioriti, E.R.Kandel, and W.A.Hendrickson (2010).
Essential role of coiled coils for aggregation and activity of Q/N-rich prions and PolyQ proteins.
  Cell, 143, 1121-1135.  
20224794 H.Goehler, A.Dröge, R.Lurz, S.Schnoegl, Y.O.Chernoff, and E.E.Wanker (2010).
Pathogenic polyglutamine tracts are potent inducers of spontaneous Sup35 and Rnq1 amyloidogenesis.
  PLoS One, 5, e9642.  
20034059 M.J.Darcy, K.Calvin, K.Cavnar, and C.C.Ouimet (2010).
Regional and subcellular distribution of HDAC4 in mouse brain.
  J Comp Neurol, 518, 722-740.  
20463240 P.Banerjee, B.P.Schoenfeld, A.J.Bell, C.H.Choi, M.P.Bradley, P.Hinchey, M.Kollaros, J.H.Park, S.M.McBride, and T.C.Dockendorff (2010).
Short- and long-term memory are modulated by multiple isoforms of the fragile X mental retardation protein.
  J Neurosci, 30, 6782-6792.  
20055418 R.He, Y.Chen, Y.Chen, A.V.Ougolkov, J.S.Zhang, D.N.Savoy, D.D.Billadeau, and A.P.Kozikowski (2010).
Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anticancer agents.
  J Med Chem, 53, 1347-1356.  
20543830 X.Liu, Q.Zhang, K.Murata, M.L.Baker, M.B.Sullivan, C.Fu, M.T.Dougherty, M.F.Schmid, M.S.Osburne, S.W.Chisholm, and W.Chiu (2010).
Structural changes in a marine podovirus associated with release of its genome into Prochlorococcus.
  Nat Struct Mol Biol, 17, 830-836.
PDB code: 2xd8
19580739 J.T.Berryman, S.E.Radford, and S.A.Harris (2009).
Thermodynamic description of polymorphism in Q- and N-rich peptide aggregates revealed by atomistic simulation.
  Biophys J, 97, 1.  
18384641 B.Marquèze-Pouey, N.Martin-Moutot, M.Sakkou-Norton, C.Lévêque, Y.Ji, V.Cornet, W.L.Hsiao, and M.Seagar (2008).
Toxicity and endocytosis of spinocerebellar ataxia type 6 polyglutamine domains: role of myosin IIb.
  Traffic, 9, 1088-1100.  
18045992 G.Paroni, N.Cernotta, C.Dello Russo, P.Gallinari, M.Pallaoro, C.Foti, F.Talamo, L.Orsatti, C.Steinkühler, and C.Brancolini (2008).
PP2A Regulates HDAC4 Nuclear Import.
  Mol Biol Cell, 19, 655-667.  
18332106 J.Backs, T.Backs, S.Bezprozvannaya, T.A.McKinsey, and E.N.Olson (2008).
Histone deacetylase 5 acquires calcium/calmodulin-dependent kinase II responsiveness by oligomerization with histone deacetylase 4.
  Mol Cell Biol, 28, 3437-3445.  
17981613 N.Majdzadeh, B.E.Morrison, and S.R.D'Mello (2008).
Class IIA HDACs in the regulation of neurodegeneration.
  Front Biosci, 13, 1072-1082.  
18563455 Y.B.Zeng, D.M.Zhang, H.Li, and H.Sun (2008).
Binding of Ni2+ to a histidine- and glutamine-rich protein, Hpn-like.
  J Biol Inorg Chem, 13, 1121-1131.  
17694086 M.Martin, R.Kettmann, and F.Dequiedt (2007).
Class IIa histone deacetylases: regulating the regulators.
  Oncogene, 26, 5450-5467.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.