Characterization of the cholesterol recognition amino acid consensus sequence of the peripheral-type benzodiazepine receptor.
Nadège Jamin,Jean-Michel Neumann,Mariano A. Ostuni,Thi Kim Ngoc Vu,Zhi-Xing Yao,Samuel Murail,Jean-Claude Robert,Christoforos Giatzakis,Vassilios Papadopoulos,Jean-Jacques Lacapère +9 more
TLDR
Structural and functional evidence is provided supporting the finding that the CRAC domain in the cytosolic carboxyl-terminal domain of PBR might be responsible for the uptake and translocation of cholesterol into the mitochondria.Abstract:
We previously defined a cholesterol recognition/interaction amino acid consensus sequence [CRAC: L/V–X (1–5)–Y–X (1–5)-R/K] in the carboxyl terminus of the peripheral-type benzodiazepine receptor (PBR), a high-affinity drug and cholesterol-binding protein present in the outer mitochondrial membrane protein. This protein is involved in the regulation of cholesterol transport into the mitochondria, the rate-determining step in steroid biosynthesis. Reconstituted wild-type recombinant PBR into proteoliposomes demonstrated high-affinity 2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinolinecarboxamide and cholesterol binding. In the present work, we functionally and structurally characterized this CRAC motif using reconstituted recombinant PBR and nuclear magnetic resonance. Deletion of the C-terminal domain of PBR and mutation of the highly conserved among all PBR amino acid sequences Y152 of the CRAC domain resulted in loss of the ability of mutant recPBR to bind cholesterol. Nuclear magnetic resonance...read more
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Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function.
Vassilios Papadopoulos,Mario Baraldi,Tomás R. Guilarte,Thomas B. Knudsen,Jean Jacques Lacapère,Peter Lindemann,Michael D. Norenberg,David J. Nutt,Abraham Weizman,Ming Rong Zhang,Moshe Gavish +10 more
TL;DR: Translocator protein (18kDa) is proposed as a new name, regardless of the subcellular localization of the protein, to represent more accurately its sub cellular role (or roles) and putative tissue-specific function (or functions).
Journal ArticleDOI
A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor.
Michael A. Hanson,Vadim Cherezov,Mark T. Griffith,Christopher B. Roth,Veli-Pekka Jaakola,Ellen Y.T. Chien,Jeffrey Velasquez,Peter Kuhn,Raymond C. Stevens +8 more
TL;DR: Temperature stability analysis using isothermal denaturation confirms that a cholesterol analog significantly enhances the stability of the receptor, and a consensus motif is defined that predicts cholesterol binding for 44% of human class A receptors, suggesting that specific sterol binding is important to the structure and stability of other G protein-coupled receptors.
Journal ArticleDOI
Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders
Rainer Rupprecht,Vassilios Papadopoulos,Gerhard Rammes,Thomas C. Baghai,Jinjiang Fan,Nagaraju Akula,Ghislaine Groyer,David H. Adams,Michael Schumacher +8 more
TL;DR: The translocator protein (18 kDa) (TSPO) is localized primarily in the outer mitochondrial membrane of steroid-synthesizing cells, including those in the central and peripheral nervous system, which is a prerequisite for steroid synthesis.
Journal ArticleDOI
How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains
TL;DR: How cholesterol interacts with membrane lipids and proteins at the molecular/atomic scale is described, with special emphasis on transmembrane domains of proteins containing either the consensus cholesterol-binding motifs CRAC and CARC or a tilted peptide.
Journal ArticleDOI
Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones.
TL;DR: The structure and function of SR-BI, the importance of the selective cholesterol transport pathway in providing cholesterol substrate for steroid biosynthesis and the role of two key proteins, StAR and PBR/TSO in facilitating cholesterol delivery to inner mitochondrial membrane sites are discussed.
References
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Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern.
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