Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein.
To identify and characterize the hormone-binding domain of the thyroid hormone receptor, we analyzed the ligand-binding capacities of proteins representing chimeras between the normal receptor and P75gag-v-erbA, the retrovirus-encoded form deficient in binding ligand. Our results show that several mutations present in the carboxy-terminal half of P75gag-v-erbA co-operate in abolishing hormone binding, and that the ligand-binding domain resides in a position analogous to that of steroid receptors. Furthermore, a point mutation that is located between the putative DNA and ligand-binding domains of P75gag-v-erbA and that renders it biologically inactive fails to affect hormone binding by the c-erbA protein. These results suggest that the mutation changed the ability of P75gag-v-erbA to affect transcription since it also had no effect on DNA binding. Our data also suggest that hormone-independent activity of P75gag-v-erbA provided a selective advantage to the avian erythroblastosis virus during the original selection for a highly oncogenic strain of the virus.
Muñoz
A
A
Differentiation Programme, EMBL, Heidelberg, FRG.
Zenke
M
M
Gehring
U
U
Sap
J
J
Beug
H
H
Vennström
B
B
D000818:Animals; D002645:Chickens; D002678:Chimera; D003001:Cloning, Molecular; D005796:Genes; D007700:Kinetics; D009154:Mutation; D010957:Plasmids; D014176:Protein Biosynthesis; D011519:Proto-Oncogenes; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D014158:Transcription, Genetic
D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D013963:Thyroid Hormones