1. Nuclear Receptor structures
Simon Folkertsma

2. Nuclear Receptors ligand-inducible transcription factors
ligands are lipophilic compounds
48 human NRs identified
key processes are regulated by NRs (homeostasis, dif-
ferentiation, embryonic development and organ physiology)
diseases: cancer, diabetes, and osteoporosis
Important target for pharmaceutical industry

3. Domain organization
DNA binding domain (DBD)
Ligand binding domain (LBD)

4. Mechanism

5. 3D Structure NR LBD
(hER)

7. Aligned structures

8. NR mechanism
apo
agonist
antagonist

9. Apo

10. NR mechanism
apo
agonist
antagonist

11. Agonist

12. NR mechanism
apo
agonist
antagonist

13. Antagonist

14. Where does the ligand bind?
Where is H12?
Where does the cofactor bind?
Is the compound an agonist or antagonist?
Can you find all twelve helices?
Are there hydrogen bonds between the ligand and the
protein?