1nq0: Difference between revisions
New page: left|200px<br /> <applet load="1nq0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nq0, resolution 2.40Å" /> '''TR Receptor Mutatio... |
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[[Image:1nq0. | [[Image:1nq0.jpg|left|200px]]<br /><applet load="1nq0" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''TR Receptor Mutations Conferring Hormone Resistance and Reduced Corepressor Release Exhibit Decreased Stability in the Nterminal LBD'''<br /> | '''TR Receptor Mutations Conferring Hormone Resistance and Reduced Corepressor Release Exhibit Decreased Stability in the Nterminal LBD'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1NQ0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 4HY and ARS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1NQ0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=4HY:'>4HY</scene> and <scene name='pdbligand=ARS:'>ARS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NQ0 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thyroid hormone receptor]] | [[Category: thyroid hormone receptor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:30:12 2008'' | ||
Revision as of 17:30, 15 February 2008
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TR Receptor Mutations Conferring Hormone Resistance and Reduced Corepressor Release Exhibit Decreased Stability in the Nterminal LBD
OverviewOverview
Resistance to thyroid hormone (RTH) syndrome is associated with mutations, in the human thyroid hormone receptor-beta (hTRbeta), many of which show, marked reduction in hormone binding. Here, we investigated the structural, consequences of two RTH mutants (A234T and R243Q), residing in the, flexible N-terminal portion of the ligand binding domain (LBD), which, exhibit modestly reduced hormone binding with impaired release of, corepressor. X-ray crystallography analyses revealed that these two RTH, mutants modulate the position of this flexible region by either altering, the movement of helix 1 (A234T) or disrupting a salt bridge (R243Q). The, subsequent increased flexibility and mobility in regions after the two, sites of mutation coincided with a disorganized LBD. Consistent with this, finding, the ability of these mutant N-terminal regions (234-260) to, recruit the remaining LBD was decreased in a ligand-dependent helix, assembly assay. Collectively, these data suggest that structural, information imparted by the flexible segment in the N-terminal LBD is, critical for overall stability of the LBD. Thus, these structural analyses, provide mechanistic insight into the etiology of RTH disease in human, TRbeta mutants that exhibit hormone binding with decreased, ligand-dependent corepressor release.
DiseaseDisease
Known diseases associated with this structure: Thyroid hormone resistance OMIM:[190160], Thyroid hormone resistance, autosomal recessive OMIM:[190160]
About this StructureAbout this Structure
1NQ0 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain., Huber BR, Desclozeaux M, West BL, Cunha-Lima ST, Nguyen HT, Baxter JD, Ingraham HA, Fletterick RJ, Mol Endocrinol. 2003 Jan;17(1):107-16. PMID:12511610
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