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Interaction of the N-terminus of ecdysone receptor isoforms with the ligand-binding domain
- Tremmel, Ch., Schaefer, M., Azoitei, A., Ruff, H., Spindler-Barth, M.
- Molecular and cellular endocrinology 2011 v.332 no.1-2 pp. 293-300
- ecdysone, fluorescence, mutation, transcription (genetics)
- Ecdysone receptor (EcR) isoforms exert different biological functions, although they vary only in their N-terminal domain. Despite identical C-termini, which mediate hormone-induced activity, the influence of ligand is isoform specific, which indicates an N/C-interaction. The position of helix 12 with and without hormone varies among isoforms and modifies N/C-interaction determined by fluorescence resonance-energy transfer (FRET), which depends on the salt bridge between helices 4 and 12 of the ligand-binding domain (LBD). Disruption of the salt bridge by mutation of K497 (helix 4) had no effect on basal N/C-interaction, but prevented the hormone-induced increase, which was partially restored by a salt bridge with reversed polarity. The heterodimerization partner Ultraspiracle (Usp) can compensate for the disruption of the salt bridge. Without ligand the AB-domains of EcR-A and EcR-B1, but not EcR-B2, interact with the LBD via K497 and repress transcriptional activity. This intramolecular cross talk between N- and C-terminus along with the position of helix 12 stabilized by K497 regulates transcriptional activity of EcR isoforms.