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2o94

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Revision as of 08:54, 18 October 2017

The 97H/F mutant Structure of a glutamine-rich domain from histone deacetylase 4

Structural highlights

2o94 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	HDAC4, KIAA0288 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[HDAC4_HUMAN] Defects in HDAC4 are the cause of brachydactyly-mental retardation syndrome (BDMR) [MIM:600430]. A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism.^[1]

Function

[HDAC4_HUMAN] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D.^[2]

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

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.

Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains.,Guo L, Han A, Bates DL, Cao J, Chen L Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4297-302. Epub 2007 Mar 5. PMID:17360518^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Williams SR, Aldred MA, Der Kaloustian VM, Halal F, Gowans G, McLeod DR, Zondag S, Toriello HV, Magenis RE, Elsea SH. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am J Hum Genet. 2010 Aug 13;87(2):219-28. doi: 10.1016/j.ajhg.2010.07.011. PMID:20691407 doi:10.1016/j.ajhg.2010.07.011
↑ Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ. HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor. Mol Cell Biol. 1999 Nov;19(11):7816-27. PMID:10523670
↑ Guo L, Han A, Bates DL, Cao J, Chen L. 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. 2007 Mar 13;104(11):4297-302. Epub 2007 Mar 5. PMID:17360518

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2o94"

@@ Line 1: / Line 1: @@
 ==The 97H/F mutant Structure of a glutamine-rich domain from histone deacetylase 4==
 <StructureSection load='2o94' size='340' side='right' caption='[[2o94]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2o94]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O94 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2O94 FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HDAC4, KIAA0288 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o94 OCA], [http://pdbe.org/2o94 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2o94 RCSB], [http://www.ebi.ac.uk/pdbsum/2o94 PDBsum]</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=2o94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o94 OCA], [http://pdbe.org/2o94 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2o94 RCSB], [http://www.ebi.ac.uk/pdbsum/2o94 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2o94 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 2o94" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Histone deacetylase|Histone deacetylase]]
 == References ==
 <references/>

2o94

From Proteopedia

Revision as of 08:54, 18 October 2017

The 97H/F mutant Structure of a glutamine-rich domain from histone deacetylase 4

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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