4UC1

High resolution crystal structure of translocator protein 18kDa (TSPO) from Rhodobacter sphaeroides (A139T Mutant) in C2 space group

Summary for 4UC1

• Entry DOI: 10.2210/pdb4uc1/pdb
• Related: 4UC2 4UC3
• Descriptor: Translocator protein TspO, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, PROTOPORPHYRIN IX, ... (7 entities in total)
• Functional Keywords: mitochondria, transport, 5 transmembrane helices, membrane protein
• Biological source: Rhodobacter sphaeroides
• Total number of polymer chains: 3
• Total formula weight: 61450.20

Authors

Li, F.,Liu, J.,Zheng, Y.,Garavito, R.M.,Ferguson-Miller, S. (deposition date: 2014-08-13, release date: 2015-02-04, Last modification date: 2023-12-27)

Primary citation

Li, F.,Liu, J.,Zheng, Y.,Garavito, R.M.,Ferguson-Miller, S.
Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism.
Science, 347:555-558, 2015

PubMed Abstract: The 18-kilodalton translocator protein (TSPO), proposed to be a key player in cholesterol transport into mitochondria, is highly expressed in steroidogenic tissues, metastatic cancer, and inflammatory and neurological diseases such as Alzheimer's and Parkinson's. TSPO ligands, including benzodiazepine drugs, are implicated in regulating apoptosis and are extensively used in diagnostic imaging. We report crystal structures (at 1.8, 2.4, and 2.5 angstrom resolution) of TSPO from Rhodobacter sphaeroides and a mutant that mimics the human Ala(147)→Thr(147) polymorphism associated with psychiatric disorders and reduced pregnenolone production. Crystals obtained in the lipidic cubic phase reveal the binding site of an endogenous porphyrin ligand and conformational effects of the mutation. The three crystal structures show the same tightly interacting dimer and provide insights into the controversial physiological role of TSPO and how the mutation affects cholesterol binding.

PubMed: 25635101
DOI: 10.1126/science.1260590

Experimental method

X-RAY DIFFRACTION (1.8 Å)