Abstract
The crystal structure of the rat alpha 1 thyroid hormone receptor ligand-binding domain bound with a thyroid hormone agonist reveals that ligand is completely buried within the domain as part of the hydrophobic core. In addition, the carboxy-terminal activation domain forms an amphipathic helix, with its hydrophobic face constituting part of the hormone binding cavity. These observations suggest a structural role for ligand, in establishing the active conformation of the receptor, that is likely to underlie hormonal regulation of gene expression for the nuclear receptors.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Allosteric Regulation
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Amino Acid Sequence
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Animals
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Binding Sites
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Computer Graphics
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Crystallography, X-Ray
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Escherichia coli
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Humans
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Ligands
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Models, Molecular
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Molecular Sequence Data
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Protein Conformation
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Rats
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Receptors, Thyroid Hormone / chemistry*
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Receptors, Thyroid Hormone / physiology
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Recombinant Proteins / chemistry
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Sequence Homology, Amino Acid
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Structure-Activity Relationship
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Thyroid Hormones / agonists
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Thyroid Hormones / chemistry*
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Thyroid Hormones / physiology
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Transcriptional Activation
Substances
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Ligands
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Receptors, Thyroid Hormone
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Recombinant Proteins
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Thyroid Hormones