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Structure of the mitochondrial translocator protein in complex with a diagnostic ligand.

ABSTRACT: The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane ? helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.

SUBMITTER: Jaremko L

PROVIDER: S-EPMC5650047 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Structure of the mitochondrial translocator protein in complex with a diagnostic ligand.

Jaremko Lukasz L Jaremko Mariusz M Giller Karin K Becker Stefan S Zweckstetter Markus M

Science (New York, N.Y.) 20140301 6177

The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structur ...[more]

PMID: 24653034

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| S-EPMC2930116 | biostudies-literature

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