Figure 3

Bleicher3.png. Ligand-receptor interactions for thyroid receptors: (a) T₃ as bound to hTRα (green) and hTRβ (magenta). All interactions are maintained between the ligand and the binding site residues in both hTR isoforms. Both Ser277 and Asn331 interact with the amino group of T₃ through their amide nitrogen, leading to similar conformations of these residues. (b) GC1 bound to TRα: multiple conformations of the Arg228 are observed. In the productive conformation there is a strong interaction with the ligand (cyan), while in non-productive conformations this residue interacts with the side-chain of Ser277. The Arg228 double conformation is observed in the first crystal form of hTRα LBD+GC1 complex (Table 1). In the intermediate conformation Arg228 interacts both with the GC1 and the Ser277 amino group (white, second hTRα LBD+GC-1 crystal form, Table 1). (c) Comparison of GC1 bound to hTRα and hTRβ. For hTRβ (magenta) only a single productive conformation of the Arg282 side-chain was observed, which resembles the productive Arg228 (hTRα) conformation (green). Arg282 (hTRβ), is strongly interacting with the ligand and its productive conformation is locked in place by the interactions with the side-chain of Asn331.