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. 1995 Jan;15(1):255–263. doi: 10.1128/mcb.15.1.255

Mouse retinoid X receptor contains a separable ligand-binding and transactivation domain in its E region.

X Leng 1, J Blanco 1, S Y Tsai 1, K Ozato 1, B W O'Malley 1, M J Tsai 1
PMCID: PMC231947  PMID: 7799932

Abstract

Steroid, thyroid, and retinoid hormones exert their biological functions by interacting with their cognate nuclear receptors. Upon binding receptors, hormones induce a protease-resistant structural change in the receptor ligand-binding domain and subsequently activate the receptors. Utilizing partial proteolysis, we have been able to delineate a region in the mouse retinoid X receptor beta (mRXR beta) required for ligand binding. A separable activation domain within the mRXR beta E region has been identified. The activation domain, which is 21 amino acids in length, is located at the extreme C terminus of mRXR beta. This domain is not required for ligand binding since removal of this sequence neither eliminates the ligand-induced, protease-resistant conformational change nor alters the ligand-enhanced DNA binding. Furthermore, deletion of this activation domain converts the receptor into a transcriptional silencer. Finally, a further truncation of 9 amino acids (for a total of 30 amino acids) from the C terminus results in a mutant which does not undergo the protease-resistant conformational change and cannot bind DNA as a homodimer. Nevertheless, this mutant is still able to form a heterodimer with the thyroid hormone receptor. Therefore, homodimerization and heterodimerization can be distinguished by this nine-amino-acid sequence.

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Selected References

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