caa a22 4500 606243070 CHVBK 20210128101322.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s12551-015-0173-7 doi (NATIONALLICENCE)springer-10.1007/s12551-015-0173-7 Disordered allostery: lessons from glucocorticoid receptor [Elektronische Daten] [Hesam Motlagh, Jeremy Anderson, Jing Li, Vincent Hilser] Allostery is a biological regulation mechanism of significant importance in cell signaling, metabolism, and disease. Although the ensemble basis of allostery has been known for years, only recently has emphasis shifted from interpreting allosteric mechanism in terms of discrete structural pathways to ones that focus on the statistical nature of the signal propagation process, providing a vehicle to unify allostery in structured, dynamic, and disordered systems. In particular, intrinsically disordered (ID) proteins (IDPs), which lack a unique, stable structure, have been directly demonstrated to exhibit allostery in numerous systems, a reality that challenges traditional structure-based models that focus on allosteric pathways. In this chapter, we will discuss the historical context of allostery and focus on studies from human glucocorticoid receptor (GR), a member of the steroid hormone receptor (SHR) family. The numerous translational isoforms of the disordered N-terminal domain of GR consist of coupled thermodynamic domains that contribute to the delicate balance of states in the ensemble and hence in vivo activity. The data are quantitatively interpreted using the ensemble allosteric model (EAM) that considers only the intrinsic and measurable energetics of allosteric systems. It is demonstrated that the EAM provides mechanistic insight into the distribution of states in solution and provides an interpretation for how certain translational isoforms of GR display enhanced and repressed transcriptional activities. The ensemble nature of allostery illuminated from these studies lends credence to the EAM and provides ground rules for allostery in all systems. International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg, 2015 Allostery nationallicence Intrinsic disorder nationallicence Glucocorticoid receptor nationallicence Protein stability nationallicence Ensemble nationallicence Motlagh Hesam T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut Anderson Jeremy T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut Li Jing T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut Hilser Vincent T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut Biophysical Reviews Springer Berlin Heidelberg 7/2(2015-06-01), 257-265 1867-2450 7:2<257 2015 7 12551 https://doi.org/10.1007/s12551-015-0173-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s12551-015-0173-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Motlagh Hesam T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Anderson Jeremy T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Li Jing T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Hilser Vincent T.C. Jenkins Department of Biophysics, Johns Hopkins University, 21218, Baltimore, MD, USA aut NATIONALLICENCE 773 0- Biophysical Reviews Springer Berlin Heidelberg 7/2(2015-06-01), 257-265 1867-2450 7:2<257 2015 7 12551