The thyroid hormone receptor recruits NCoR via widely spaced receptor-interacting domains.
The nuclear receptor corepressor (NCoR) interacts with the DNA-bound thyroid receptor (TR) homodimer through two of its three receptor-interacting domains (RIDs). One of these RIDs must be the most N-terminal, termed N3, which preferentially works with the next closest RID, N2. Interestingly, the spacing between the RIDs is conserved between species such that N3 and N2 are separated by approximately 120 aa, while the spacing between N2 and N1 is around 205 aa, suggesting that distance plays a role in the specificity of N3 and N2. Herein, we demonstrate that even when spaced by 122 aa N2 and N1 cannot mediate recruitment to the TR homodimer. Furthermore, N3 is able to function with either N2 or N1 at distances as small as 45 aa and as large as 240 aa. Thus, specificity of NCoR recruitment to the TR is dictated by the amino acid sequence of N3, and not by the distance separating it from other RIDs. Furthermore, the wide spacing of the NCoR RIDs likely allows for potential flexibility in the DNA-bound TR complex in its ability to recruit NCoR.
Astapova
Inna
I
Division of Endocrinology, Metabolism and Diabetes, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Dordek
Melissa F
MF
Hollenberg
Anthony N
AN
D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D015203:Reproducibility of Results; D047488:Retinoid X Receptors / Q000378:metabolism; D013045:Species Specificity; D020798:Two-Hybrid System Techniques
C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D047488:Retinoid X Receptors