2o94

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(New page: 200px<br /> <applet load="2o94" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o94, resolution 3.000&Aring;" /> '''The 97H/F mutant S...)
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[[Image:2o94.gif|left|200px]]<br />
 
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<applet load="2o94" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2o94, resolution 3.000&Aring;" />
 
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'''The 97H/F mutant Structure of a glutamine-rich domain from histone deacetylase 4'''<br />
 
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==Overview==
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==The 97H/F mutant Structure of a glutamine-rich domain from histone deacetylase 4==
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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.
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<StructureSection load='2o94' size='340' side='right'caption='[[2o94]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2o94]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=2O94 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2o94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o94 OCA], [https://pdbe.org/2o94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o94 RCSB], [https://www.ebi.ac.uk/pdbsum/2o94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o94 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/HDAC4_HUMAN HDAC4_HUMAN] Defects in HDAC4 are the cause of brachydactyly-mental retardation syndrome (BDMR) [MIM:[https://omim.org/entry/600430 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.<ref>PMID:20691407</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/HDAC4_HUMAN 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.<ref>PMID:10523670</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/o9/2o94_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/main_output.php?pdb_ID=2o94 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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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.
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==About this Structure==
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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<ref>PMID:17360518</ref>
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2O94 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2O94 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17360518 17360518]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2o94" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Bates, D.L.]]
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[[Category: Chen, L.]]
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[[Category: Guo, L.]]
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[[Category: Han, A.]]
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[[Category: alpha helix]]
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[[Category: polar zipper]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:07:55 2007''
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==See Also==
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*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Bates DL]]
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[[Category: Chen L]]
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[[Category: Guo L]]
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[[Category: Han A]]

Current revision

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

PDB ID 2o94

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