60. Based on the structural regions of a nuclear receptorshown in the diagram, the following predictions weremade.
A) Region F is responsible for binding to ligands and contains two zinc finger-like binding motifs
B) Receptors with A/B domains generally associate with chaperones and do not bind to DNA.
C) Region E indicate that receptors associate with chaperones which protect the nuclear hormone receptors.
D) Region C contains the P-box and the D-box required for dimerization of the receptor

and creates contact with DNA phosphate backbone.
Which one of the following is true?
(1) A and B       (2) B and C
(3) Band D       (4) C and D

Nuclear Receptor Structural Domains: Correct Functional Assignments

Introduction

Nuclear receptors (NRs) are modular transcription factors that regulate gene expression in response to ligand binding. Understanding their structural domains is crucial to grasp their mechanism of action. The common functional domains are typically labeled A-F or A/B, C, D, E, and sometimes F, each with distinct roles.

Analysis of the Predictions

• A) Region F is responsible for binding to ligands and contains two zinc finger-like binding motifs

  • Incorrect. The ligand-binding domain (LBD) is region E; zinc fingers for DNA binding reside in region C. Region F is typically variable and at the C-terminus without these key motifs.

• B) Receptors with A/B domains generally associate with chaperones and do not bind DNA.

  • Incorrect. The A/B (or N-terminal) region contains the activation function-1 (AF-1) domain and is highly variable. Chaperone association occurs mainly at the ligand-binding domain, not the A/B domain. DNA-binding is through domain C.

• C) Region E indicate that receptors associate with chaperones which protect the nuclear hormone receptors.

  • Correct. Region E is the ligand-binding domain where chaperone (e.g., Hsp90) binding occurs to maintain receptor proper folding and regulation before ligand binding.

• D) Region C contains the P-box and the D-box required for dimerization of the receptor and creates contact with DNA phosphate backbone.

  • Partially correct. Region C is the DNA-binding domain containing two zinc fingers. The P-box is essential for DNA sequence specificity, and D-box mediates dimerization. Interaction with DNA phosphate backbone occurs as part of DNA binding.

Correct Option

(4) C and D

Summary Table

Additional Notes

• The P-box and D-box within the zinc finger domain regulate DNA binding specificity and receptor dimerization respectively.

• Chaperone association primarily occurs at the LBD (region E) to keep receptors in inactive but activatable conformations.