DERIVATIVE DATA FOR LIGAND BINDING DOMAIN (LBD) OF THYROID HORMONE RECP

$143,176P41FY2002RRNIH

Stanford University, Stanford CA

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Abstract

Thyroid hormones are involved in the regulation of both development and metabolism. The major hormone -triiodothyronine (T3), binds a nuclear receptor (TR) which regulates the transcription of the gene products that mediate hormone response. Binding of T3 by TR induces a conformational change that alters the regulatory properties of the receptor. Our understanding of the mechanism by which hormone binding regulates receptor activity would be advanced by a structure of the TR ligand binding domain with T3 bound, at 2.0E resolution. The domain consists largely of alpha helices, and reveals an unexpected binding mode for hormone, in which the hormone buried within the receptor as part of the hydrophobic core.

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