Insight Into Molecular Determinants of T3 vs T4 Recognition From Mutations in Thyroid Hormone Receptor α and β.

ABSTRACT:

Context

The two major forms of circulating thyroid hormones (THs) are T3 and T4. T3 is regarded as the biologically active hormone because it binds to TH receptors (TRs) with greater affinity than T4. However, it is currently unclear what structural mechanisms underlie this difference in affinity.

Objective

Prompted by the identification of a novel M256T mutation in a resistance to TH (RTH)α patient, we investigated Met256 in TRα1 and the corresponding residue (Met310) in TRβ1, residues previously predicted by crystallographic studies in discrimination of T3 vs T4.

Methods

Clinical characterization of the RTHα patient and molecular studies (in silico protein modeling, radioligand binding, transactivation, and receptor-cofactor studies) were performed.

Results

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SUBMITTER: Wejaphikul K 

PROVIDER: S-EPMC6599431 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature