3d57: Difference between revisions
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==TR Variant D355R== | ==TR Variant D355R== | ||
<StructureSection load='3d57' size='340' side='right' caption='[[3d57]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='3d57' size='340' side='right' caption='[[3d57]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4HY:[4-(4-HYDROXY-3-IODO-PHENOXY)-3,5-DIIODO-PHENYL]-ACETIC+ACID'>4HY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4HY:[4-(4-HYDROXY-3-IODO-PHENOXY)-3,5-DIIODO-PHENYL]-ACETIC+ACID'>4HY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">7068, ERBA2, NR1A2, THR1, THRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">7068, ERBA2, NR1A2, THR1, THRB ([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=3d57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d57 OCA], [http://pdbe.org/3d57 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3d57 RCSB], [http://www.ebi.ac.uk/pdbsum/3d57 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=3d57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d57 OCA], [http://pdbe.org/3d57 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3d57 RCSB], [http://www.ebi.ac.uk/pdbsum/3d57 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3d57 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d5/3d57_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d5/3d57_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 3d57" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3d57" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Thyroid hormone receptor|Thyroid hormone receptor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Human]] | [[Category: Human]] | ||
[[Category: Jouravel, N]] | [[Category: Jouravel, N]] | ||
[[Category: Alternative splicing]] | |||
[[Category: D355r mutant]] | [[Category: D355r mutant]] | ||
[[Category: Deafness]] | [[Category: Deafness]] | ||
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[[Category: Metal-binding]] | [[Category: Metal-binding]] | ||
[[Category: Nucleus]] | [[Category: Nucleus]] | ||
[[Category: Polymorphism]] | |||
[[Category: Receptor]] | [[Category: Receptor]] | ||
[[Category: Thyroid hormone receptor]] | [[Category: Thyroid hormone receptor]] | ||
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[[Category: Transcription receptor]] | [[Category: Transcription receptor]] | ||
[[Category: Transcription regulation]] | [[Category: Transcription regulation]] | ||
[[Category: Zinc]] | |||
[[Category: Zinc-finger]] | [[Category: Zinc-finger]] | ||
Revision as of 12:14, 14 November 2018
TR Variant D355RTR Variant D355R
Structural highlights
Disease[THB_HUMAN] Defects in THRB are the cause of generalized thyroid hormone resistance (GTHR) [MIM:188570]. GTHR is a disease characterized by goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. GTHR patients also have high levels of circulating thyroid hormones (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] Defects in THRB are the cause of generalized thyroid hormone resistance autosomal recessive (GTHRAR) [MIM:274300]. An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. Defects in THRB are the cause of selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]; also known as familial hyperthyroidism due to inappropriate thyrotropin secretion. PRTH is a variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established.[19] [20] Function[THB_HUMAN] High affinity receptor for triiodothyronine.[21] 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 PubMedProtein quality and stability are critical during protein purification for X-ray crystallography. A target protein that is easy to manipulate and crystallize becomes a valuable product useful for high-throughput crystallography for drug design and discovery. In this work, a single surface mutation, D355R, was shown to be crucial for converting the modestly stable monomeric ligand binding domain of the human thyroid hormone receptor (TR LBD) into a stable dimer. The structure of D335R TR LBD mutant was solved using X-ray crystallography and refined to 2.2 A resolution with R(free)/R values of 24.5/21.7. The crystal asymmetric unit reveals the TR dimer with two molecules of the hormone-bound LBD related by twofold symmetry. The ionic interface between the two LBDs comprises residues within loop H10-H11 and loop H6-H7 as well as the C-terminal halves of helices 8 of both protomers. Direct intermolecular contacts formed between the introduced residue Arg 355 of one TR molecule and Glu 324 of the second molecule become a part of the extended dimerization interface of 1330 A(2) characteristic for a strong complex assembly that is additionally strengthened by buffer solutes. Proteins 2008. (c) 2008 Wiley-Liss, Inc. Molecular basis for dimer formation of TRbeta variant D355R.,Jouravel N, Sablin E, Togashi M, Baxter JD, Webb P, Fletterick RJ Proteins. 2008 Sep 17. PMID:18798561[22] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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