1nq2
From Proteopedia
(New page: 200px<br /> <applet load="1nq2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nq2, resolution 2.4Å" /> '''Two RTH Mutants with...) |
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caption="1nq2, resolution 2.4Å" /> | caption="1nq2, resolution 2.4Å" /> | ||
'''Two RTH Mutants with Impaired Hormone Binding'''<br /> | '''Two RTH Mutants with Impaired Hormone Binding'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1NQ2 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 NA, 4HY and ARS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1NQ2 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=NA:'>NA</scene>, <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=1NQ2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: ligand binding domain]] | [[Category: ligand binding domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:30:18 2008'' |
Revision as of 14:30, 15 February 2008
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Two RTH Mutants with Impaired Hormone Binding
Contents |
Overview
Resistance to hormones is commonly due to mutations in genes encoding, receptors. Resistance to thyroid hormone is due mostly to mutations of the, beta-form of the human (h) thyroid hormone receptor (hTRbeta). We, determined x-ray crystal structures of two hTRbeta ligand-binding domains, (LBDs), Ala 317 Thr and Arg 316 His. Amino acids 316 and 317 form part of, the hormone-binding pocket. The methyl of Ala 317, contacting iodine, sculpts the T3 hormone-binding pocket. Arg 316 is not in direct contact, with T3 and has an unknown role in function. Remarkably, the Arg forms, part of an unusual buried polar cluster in hTRbeta. Although the identity, of the amino acids changes, the polar cluster appears in all nuclear, receptors. In spite of the differing roles of 316 and 317, both resistance, to thyroid hormone mutants display decreased T3 affinity and weakened, transcriptional activation. The two mutants differ in that the Arg 316 His, receptor does not form TR-TR homodimers on DNA. 3,5,3'-Triiodothyroacetic, acid is bound to both receptors. Thr 317 repositions, 3,5,3'-triiodothyroacetic acid distending the face of the receptor that, binds coregulators. Arg 316 forms two hydrogen bonds with helix 1. Both, are lost with mutation to His displacing helix 1 of the LBD and, disordering the loop after helix 1. The stability of the helix 1, deriving, in part from the buried polar cluster, is important for hormone binding, and formation of TR dimers. The observation that the Arg 316 His mutation, affects these functions implies a role for helix 1 in linking hormone, binding to the DNA-binding domain-LBD configuration.
Disease
Known diseases associated with this structure: Thyroid hormone resistance OMIM:[190160], Thyroid hormone resistance, autosomal recessive OMIM:[190160]
About this Structure
1NQ2 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Two resistance to thyroid hormone mutants with impaired hormone binding., Huber BR, Sandler B, West BL, Cunha Lima ST, Nguyen HT, Apriletti JW, Baxter JD, Fletterick RJ, Mol Endocrinol. 2003 Apr;17(4):643-52. Epub 2003 Jan 16. PMID:12554782
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