Related Experiment Video
Updated: Nov 19, 2025

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling
Nelson E Bruno1, Jerome C Nwachukwu1, Sathish Srinivasan1
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Abstract:
Glucocorticoids display remarkable anti-inflammatory activity, but their use is limited by on-target adverse effects including insulin resistance and skeletal muscle atrophy. We used a chemical systems biology approach, ligand class analysis, to examine ligands designed to modulate glucocorticoid receptor activity through distinct structural mechanisms. These ligands displayed diverse activity profiles, providing the variance required to identify target genes and coregulator interactions that were highly predictive of their effects on myocyte glucose disposal and protein balance. Their anti-inflammatory effects were linked to glucose disposal but not muscle atrophy. This approach also predicted selective modulation in vivo, identifying compounds that were muscle-sparing or anabolic for protein balance and mitochondrial potential. Ligand class analysis defined the mechanistic links between the ligand-receptor interface and ligand-driven physiological outcomes, a general approach that can be applied to any ligand-regulated allosteric signaling system.
Related Concept Videos
Chemical Signaling in the Endocrine System
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...
Cell Signaling in Plants
Signal Transduction: Overview
Typically, signal transduction involves three...
Cell-surface Signaling
Insulin: The Receptor and Signaling Pathways
Amplifying Signals via Enzymatic Cascade

