Ecdysone Receptor - Structure

Structure

The receptor is a non-covalent heterodimer of two proteins, the EcR protein and ultraspiracle protein (USP). These nuclear hormone receptor proteins are the insect orthologs of the mammalian farnesoid X receptor (FXR) and retinoid X receptor (RXR) proteins, respectively. Based on sequence homology considerations, some researchers reserve the term USP for the EcR partner from lepidopteran and dipteran insects, and use RXR in all other instances.

EcR and USP share the multi-domain architecture common to all nuclear hormone receptors, namely an N-terminal transcriptional activation domain (A/B domain), a DNA-binding domain (C domain, highly conserved between receptors), a linker region (D region), a ligand-binding domain (E domain, moderately conserved), and in some cases a distinct C-terminal extension (F-domain). The DNA-binding domains of EcR and USP recognise specific short sequences in DNA, and mediate the binding of the heterodimer to these ecdysone response elements (ECREs) in the promoters of ecdysone-responsive genes.

The ecdysteroid-binding pocket is located in the ligand binding domain of the EcR subunit, but EcR must be dimerised with a USP (or with an RXR) for high-affinity ligand binding to occur. In such circumstances, the binding of an agonist ligand triggers a conformational change in the C-terminal part of the EcR ligand-binding domain that leads to transcriptional activation of genes under ECRE control. There is also a ligand-binding pocket in the corresponding domain of USP. Its natural ligand remains uncertain, and USPs appear to be locked permanently in an inactive conformation.

X-ray crystal structures have been determined for several heterodimeric DNA-binding domains and ligand-binding domains from ecdysone receptors.