The RXR-alpha C-terminus T462 is a NMR sensor for coactivator peptide binding
Lu, Jianyun; Chen, Minghe; DeKoster, Gregory T.; Cistola, David P.; Li, Ellen
The C-terminal activation function-2 (AF-2) helix plays a crucial role in retinoid X receptor alpha (RXRα)-mediated gene expression. Here, we report a nuclear magnetic resonance (NMR) study of the RXRα ligand-binding domain complexed with 9-cis-retinoic acid and a glucocorticoid receptorinteracting protein 1 peptide. The AF-2 helix and most of the C-terminal residues were undetectable due to a severe line-broadening effect. Due to its outstanding signal-to-noise ratio, the C-terminus residue, threonine 462 (T462) exhibited two distinct crosspeaks during peptide titration, suggesting that peptide binding was in a slow exchange regime on the chemical shift timescale. Consistently, the Kd derived from T462 intensity decay agreed with that derived from isothermal titration calorimetry. Furthermore, the exchange contribution to the 15N transverse relaxation rate was measurable in either T462 or the bound peptide. These results suggest that T462 is a sensor for coactivator binding and is a potential probe for AF-2 helix mobility. Originally published Biochemical and Biophysical Research Communications, Vol. 366, No. 4, Feb 2008
Lu, Jianyun, & Chen, Minghe, & DeKoster, Gregory T., & Cistola, David P., & Li, Ellen. (February 2008). The RXR-alpha C-terminus T462 is a NMR sensor for coactivator peptide binding. , (. Retrieved from http://hdl.handle.net/10342/3341
Lu, Jianyun, and Chen, Minghe, and DeKoster, Gregory T., and Cistola, David P., and Li, Ellen. "The RXR-alpha C-terminus T462 is a NMR sensor for coactivator peptide binding". . . (.), February 2008. May 20, 2022. http://hdl.handle.net/10342/3341.
Lu, Jianyun and Chen, Minghe and DeKoster, Gregory T. and Cistola, David P. and Li, Ellen, "The RXR-alpha C-terminus T462 is a NMR sensor for coactivator peptide binding," , no. (February 2008), http://hdl.handle.net/10342/3341 (accessed May 20, 2022).
Lu, Jianyun, Chen, Minghe, DeKoster, Gregory T., Cistola, David P., Li, Ellen. The RXR-alpha C-terminus T462 is a NMR sensor for coactivator peptide binding. . February 2008; () . http://hdl.handle.net/10342/3341. Accessed May 20, 2022.
East Carolina University