Thyroid Hormone Receptor Mutations in Cancer and Resistance to Thyroid Hormone: Perspective and Prognosis

Figure 2

Domain comparison of different TR isoforms and schematic of DNA- and ligand-binding domain crystal structures. Each TR isoform is represented as a horizontal bar, from N to C termini. Total amino acid length is indicated at right [35, 36]. Within a given isoform, the location of each domain is lettered (A/B, C, D, and E/F). Identical domains of TRβ1 and TRβ2 are shown in matching colors. Note the unique A/B domain of TRβ2. Below left depicts the structure of the TR DNA-binding domain. α-helical domains are represented as purple cylinders and coordinating zinc atoms (Zn) as silver spheres. Below right depicts two conformations (−T3 and +T3) of the TR ligand-binding domain, which is composed of 12 𝛼 helices; the 12th helix (dark blue cylinder, labeled “H12”) contains the ligand-dependent activation domain. In the −T3 conformation, helix 12 is in an extended position and the corepressor binding groove is filled with the CoRNR-box helical motifs found in SMRT and NCoR (red cylinder, labeled “CoR”). In the +T3 conformation, helix 12 has rotated to close around T3 hormone ligand (shown in yellow), and a novel docking surface for the LXXLL motifs of a transcriptional coactivator has formed (green cylinder, labeled “CoA”).