Nuclear Receptor structures

Simon FolkertsmaSimon Folkertsma

Nuclear Receptors

ligand-inducible transcription factorsligands are lipophilic compounds48 human NRs identifiedkey processes are regulated by NRs (homeostasis, dif-ferentiation, embryonic development and organ physiology)diseases: cancer, diabetes, and osteoporosis

Important target for pharmaceutical industry

Domain organization

DNA binding domain (DBD) Ligand binding domain (LBD)

Mechanism

3D Structure NR LBD

(hER)

Aligned structuresAligned structures

NR mechanism

apo agonist antagonist

Apo

NR mechanism

apo agonist antagonist

Agonist

NR mechanism

apo agonist antagonist

Antagonist

- 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?