title: 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.
authors: Department of Biochemistry and Molecular Biology, Michigan State University , East Lansing, Michigan 48824, United States.
authors: Fei
authors: F
authors: Li
authors: Jian
authors: J
authors: Liu
authors: Lance
authors: L
authors: Valls
authors: Carrie
authors: C
authors: Hiser
authors: Shelagh
authors: S
authors: Ferguson-Miller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020355:Cholates / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D030562:Databases, Protein; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D018079:Receptors, GABA / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D012984:Software
chemical_list: D001426:Bacterial Proteins; D020355:Cholates; D033681:Mitochondrial Membrane Transport Proteins; D018079:Receptors, GABA; C499229:TSPO protein, human; D002784:Cholesterol
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