4JGV: Crystal Structure Of Human Nur77 Ligand-binding Domain In Complex With Thpn

Autophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds. The autophagic cascade comprises TR3 translocation to mitochondria through interaction with the mitochondrial outer membrane protein Nix, crossing into the mitochondrial inner membrane through Tom40 and Tom70 channel proteins, dissipation of mitochondrial membrane potential by the permeability transition pore complex ANT1-VDAC1 and induction of autophagy. This process leads to excessive mitochondria clearance and irreversible cell death. It implicates a new approach to melanoma therapy through activation of a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death.
PDB ID: 4JGVDownload
MMDB ID: 116052
PDB Deposition Date: 2013/3/4
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 3.01  Å
Source Organism:
Similar Structures:
Biological Unit for 4JGV: dimeric; determined by author and by software (PISA)
Molecular Components in 4JGV
Label Count Molecule
Proteins (2 molecules)
Nuclear Receptor Subfamily 4 Group a Member 1(Gene symbol: NR4A1)
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB