Related Experiment Video

Updated: Aug 17, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

The nuclear xenobiotic receptor pregnane X receptor: recent insights and new challenges

Jillian Orans1, Denise G Teotico, Matthew R Redinbo

  • 1Department of Chemistry, CB 3290, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.

Molecular Endocrinology (Baltimore, Md.)
|June 18, 2005
PubMed

Insights

The pregnane X receptor (PXR) is a key transcription factor regulating metabolism. Its unique structural flexibility allows it to bind diverse ligands, influencing protective gene expression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • The nuclear receptor pregnane X receptor (PXR) is a crucial regulator of xenobiotic and endobiotic metabolism.
  • PXR responds to a wide range of chemically diverse ligands, including drugs and endogenous compounds.
  • The structural basis for PXR's ligand-binding promiscuity remains incompletely understood.

Purpose of the Study:

  • To investigate the structural mechanisms underlying PXR's ability to bind diverse ligands.
  • To explore the role of mobile regions within the PXR ligand-binding domain.
  • To review the functional significance of PXR in biological pathways and identify future research directions.

Main Methods:

  • Structural analysis of the PXR ligand-binding domain.
  • Examination of ligand-induced conformational changes.
  • Review of existing literature on PXR function and regulation.

Main Results:

  • Mobile regions, novel to the nuclear receptor ligand-binding domain fold, are critical for PXR's promiscuous ligand binding.
  • These flexible regions enable PXR to accommodate a variety of small and large agonists.
  • PXR's structural adaptability is central to its broad regulatory functions.

Conclusions:

  • The structural plasticity of PXR, particularly its mobile regions, explains its ability to bind diverse ligands.
  • Understanding PXR structure-function relationships is vital for comprehending its role in metabolism and drug response.
  • Further research into PXR's structural dynamics and biological roles is warranted.

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...