Mouse retinoid X receptor contains a separable ligand-binding and transactivation domain in its E region.
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.
Leng
X
X
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Blanco
J
J
Tsai
S Y
SY
Ozato
K
K
O'Malley
B W
BW
Tsai
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D010450:Endopeptidases / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry*; D047488:Retinoid X Receptors; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D015533:Transcriptional Activation; D014212:Tretinoin / Q000378:metabolism
D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D047488:Retinoid X Receptors; D015534:Trans-Activators; D014157:Transcription Factors; D014212:Tretinoin; D010450:Endopeptidases