Article
Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain.
Molecular endocrinology (Baltimore, Md.) - 1 Jan 2003
Huber B Russell, Desclozeaux Marion, West Brian L, Cunha-Lima Suzana T, Nguyen Hoa T, Baxter John D, Ingraham Holly A, Fletterick Robert J
Abstract excerpt
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...
Topics
- Binding Sites
- Crystallography, X-Ray
- Humans
- Ligands
- Models, Molecular
- Mutation
- Protein Structure, Tertiary
- Receptors, Thyroid Hormone
- Repressor Proteins
- Structure-Activity Relationship