58. Heat shock protein binding region is located in which one of the following domains of glucocorticoid receptor protein?
(1) DNA-binding       (2) Ligand-binding
(3) N-terminal         (4) Hinge region

Heat Shock Protein Binding Region in Glucocorticoid Receptor Protein

Overview
The heat shock protein 90 (Hsp90) binding region of the glucocorticoid receptor (GR) is primarily located within the receptor’s ligand-binding domain (LBD), which is its C-terminal region. This association is essential for maintaining the receptor in a stable, inactive conformation in the cytoplasm before hormone binding.

Key Points

• The unliganded GR exists in the cytoplasm as part of a heteromeric complex involving Hsp90, Hsp70, and other co-chaperones.

• Hsp90 binds primarily through the carboxy-terminal ligand-binding domain of GR.

• Binding of the hormone to the ligand-binding domain induces dissociation from Hsp90, allowing receptor activation, nuclear translocation, and subsequent gene regulation.

• The interaction with Hsp90 helps maintain the receptor in a conformation competent to bind the hormone with high affinity.

Supporting Evidence

Research by Yang and DeFranco (1996) [PubMed 8838140] demonstrated that Hsp90 associates with the glucocorticoid receptor predominantly via the ligand-binding domain. Stabilization of the GR/Hsp90 complex inhibits nuclear import and activation, highlighting the functional significance of this binding site. Other studies confirm that hormone-induced conformational changes in the ligand-binding domain promote Hsp90 dissociation and receptor activation.

Implications

Understanding the localization of the Hsp90 binding region provides insight into:

• How steroid receptors are held inactive before ligand binding.

• Mechanisms governing receptor folding, stability, and hormone affinity.

• Potential pharmaceutical targeting of chaperone interactions to modulate receptor activity.

Summary

The heat shock protein binding region in the glucocorticoid receptor lies within the ligand-binding domain (option 2). This domain is critical for interaction with Hsp90, which regulates receptor stability and hormone responsiveness.

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Answer: (2) Ligand-binding domain

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