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4KZJ

Crystal Structure of TR3 LBD L449W Mutant

Summary for 4KZJ
Entry DOI10.2210/pdb4kzj/pdb
Related4JGV 4KZI 4KZM
DescriptorNuclear receptor subfamily 4 group A member 1, GLYCEROL (3 entities in total)
Functional Keywordsorphan nuclear receptor, transcription
Biological sourceHomo sapiens (human)
Total number of polymer chains2
Total formula weight57912.99
Authors
Li, F.,Zhang, Q.,Li, A.,Tian, X.,Cai, Q.,Wang, W.,Wang, Y.,Chen, H.,Xing, Y.,Wu, Q.,Lin, T. (deposition date: 2013-05-30, release date: 2013-12-18, Last modification date: 2024-03-20)
Primary citationWang, W.J.,Wang, Y.,Chen, H.Z.,Xing, Y.Z.,Li, F.W.,Zhang, Q.,Zhou, B.,Zhang, H.K.,Zhang, J.,Bian, X.L.,Li, L.,Liu, Y.,Zhao, B.X.,Chen, Y.,Wu, R.,Li, A.Z.,Yao, L.M.,Chen, P.,Zhang, Y.,Tian, X.Y.,Beermann, F.,Wu, M.,Han, J.,Huang, P.Q.,Lin, T.,Wu, Q.
Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway.
Nat.Chem.Biol., 10:133-140, 2014
Cited by
PubMed Abstract: 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.
PubMed: 24316735
DOI: 10.1038/nchembio.1406
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.12 Å)
Structure validation

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