Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28510173
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biophys+Rev
2015 ; 7
(2
): 257-265
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Disordered allostery: lessons from glucocorticoid receptor
#MMPMID28510173
Motlagh HN
; Anderson JA
; Li J
; Hilser VJ
Biophys Rev
2015[Jun]; 7
(2
): 257-265
PMID28510173
show ga
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.
free
free
free
