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1nq2

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{{STRUCTURE_1nq2| PDB=1nq2 | SCENE= }}
{{STRUCTURE_1nq2| PDB=1nq2 | SCENE= }}
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'''Two RTH Mutants with Impaired Hormone Binding'''
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===Two RTH Mutants with Impaired Hormone Binding===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12554782 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12554782}}
==About this Structure==
==About this Structure==
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[[Category: Alpha helical]]
[[Category: Alpha helical]]
[[Category: Ligand binding domain]]
[[Category: Ligand binding domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:50:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:24:16 2008''

Revision as of 18:24, 28 July 2008

Image:1nq2.png

Template:STRUCTURE 1nq2

Two RTH Mutants with Impaired Hormone Binding

Template:ABSTRACT PUBMED 12554782

About this Structure

1NQ2 is a Single protein structure of sequence from Homo sapiens. 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

Page seeded by OCA on Mon Jul 28 21:24:16 2008

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