Unknown

Dataset Information

0

Identification of a key cholesterol binding enhancement motif in translocator protein 18 kDa.


ABSTRACT: Translocator protein 18 kDa (TSPO) in the mitochondrial outer membrane has been implicated in cholesterol transport regulating steroidogenesis. A human single polymorphism associated with anxiety disorders (A147T) and reduced pregnenolone production is adjacent to TSPO's cholesterol binding motif. In a mutant mimicking this polymorphism, we observe a lower level of binding of cholesterol. Further, three residues preceding A147 are more hydrophilic in a bacterial TSPO that has an affinity for cholesterol 1000-fold lower than that of the human form. Converting these residues to the human form in the bacterial homologue strikingly increases the affinity for cholesterol. An important role for this extended motif is further supported by covariance analysis.

SUBMITTER: Li F 

PROVIDER: S-EPMC5125615 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Identification of a key cholesterol binding enhancement motif in translocator protein 18 kDa.

Li Fei F   Liu Jian J   Valls Lance L   Hiser Carrie C   Ferguson-Miller Shelagh S  

Biochemistry 20150210 7


Translocator protein 18 kDa (TSPO) in the mitochondrial outer membrane has been implicated in cholesterol transport regulating steroidogenesis. A human single polymorphism associated with anxiety disorders (A147T) and reduced pregnenolone production is adjacent to TSPO's cholesterol binding motif. In a mutant mimicking this polymorphism, we observe a lower level of binding of cholesterol. Further, three residues preceding A147 are more hydrophilic in a bacterial TSPO that has an affinity for cho  ...[more]

Similar Datasets

| S-EPMC3161826 | biostudies-literature
| S-EPMC8029074 | biostudies-literature
| S-EPMC4567528 | biostudies-literature
| S-EPMC5125027 | biostudies-literature
| S-EPMC9085532 | biostudies-literature
| S-EPMC3367231 | biostudies-literature
| S-EPMC10468775 | biostudies-literature
| S-EPMC3777621 | biostudies-literature
| S-EPMC3323305 | biostudies-literature
| S-EPMC10172718 | biostudies-literature