kojetin laboratory

Nuclear Receptor Structural Pharmacology

Structure.
Dynamics.
Function.

We explore how nuclear receptors sense small molecules and regulate gene expression.

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PPARγ with Rosiglitazone and MED1 coactivator peptide, PDB 6ONJ.
MED1 coactivator peptide Rosiglitazone agonist PPARγ ligand-binding domain
MOLECULAR INTERACTIONS PDB 6ONJ ↗ Experimental structure. Assembly is schematic.

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Ligand recognition

Small molecules.
Specific effects.

Ligands bind within the receptor’s orthosteric pocket. We investigate how their interactions influence receptor activity and pharmacology.

Protein interactions

A meeting of
molecules.

Ligand binding reshapes the receptor surface recognized by transcriptional coregulator proteins, linking ligand recognition to transcription. Here, rosiglitazone-bound PPARγ LBD recruits a MED1 coactivator peptide at its AF-2 surface.

Conformational regulation

Beyond a
single structure.

Proteins sample conformational ensembles. We combine NMR spectroscopy and complementary structure–function methods to connect ligand-dependent changes in protein dynamics to molecular interactions and nuclear receptor function.

Functional regulation

From structure
to cellular function.

We test structure–function findings in cells to determine how ligand-dependent molecular interactions control receptor activity, transcription, gene expression, and cell fate.

Illustrated white adipocyte in cutaway: a large gold lipid droplet, a teal nucleus at the left edge, and mitochondria and endoplasmic reticulum in the surrounding cytoplasm.
CELLULAR CONTEXT · Adipocyte. Nucleus, lipid droplet, and surrounding cytoplasm. Conceptual illustration; not to scale.
Mechanism informed chemical biology

Mechanisms that
guide discovery.

We seek to translate our basic discoveries into next-generation chemical tools and therapeutics, using molecular mechanisms to guide ligand design and development.

CHEMICAL TOOLS, MECHANISM OF ACTION, AND DISCOVERY. Mechanistic insights guide next-generation chemical tools and therapeutics.
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The questions that drive us

How do molecular interactions
become biological responses?

We study the molecular mechanisms of nuclear receptor function. By connecting protein structure, conformational dynamics, pharmacology, and cell biology, we seek to understand how ligands and protein interactions shape nuclear receptor transcriptional regulation, gene expression, and cell fate.

Our research explores...

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Nuclear receptor structural and molecular pharmacology

How small molecules (endogenous lipids, synthetic ligands, and FDA-approved drugs) change the activity of these therapeutically important transcription factors.

Conformational dynamics and ensembles

How changes in structural motions (dynamics) connect ligand binding to shifting nuclear receptor conformational ensembles and changes in function.

Receptor partnerships

How ligand-dependent nuclear receptor self and partner (heterodimer) interactions create distinct pharmacological responses.

Integrative structural biology to function

We use integrative computational and experimental structure–function methods that connect atomic and molecular insights into cellular function and ligand discovery.

Our latest publications

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From the lab

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Science is a shared pursuit

Bring your curiosity.

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