Artículo
A mirror code for protein-cholesterol interactions in the two leaflets of biological membranes
Fantini, Jacques; Di Scala, Coralie; Evans, Luke S.; Williamson, Philip T. F.; Barrantes, Francisco Jose
Fecha de publicación:
02/2016
Editorial:
Nature Publishing Group
Revista:
Scientific Reports
e-ISSN:
2045-2322
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Cholesterol controls the activity of a wide range of membrane receptors through specific interactions and identifying cholesterol recognition motifs is therefore critical for understanding signaling receptor function. The membrane-spanning domains of the paradigm neurotransmitter receptor for acetylcholine (AChR) display a series of cholesterol consensus domains (referred to as “CARC”). Here we use a combination of molecular modeling, lipid monolayer/mutational approaches and NMR spectroscopy to study the binding of cholesterol to a synthetic CARC peptide. The CARC-cholesterol interaction is of high affinity, lipid-specific, concentration-dependent, and sensitive to single-point mutations. The CARC motif is generally located in the outer membrane leaflet and its reverse sequence CRAC in the inner one. Their simultaneous presence within the same transmembrane domain obeys a “mirror code” controlling protein-cholesterol interactions in the outer and inner membrane leaflets. Deciphering this code enabled us to elaborate guidelines for the detection of cholesterol-binding motifs in any membrane protein. Several representative examples of neurotransmitter receptors and ABC transporters with the dual CARC/CRAC motifs are presented. The biological significance and potential clinical applications of the mirror code are discussed.
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Fantini, Jacques; Di Scala, Coralie; Evans, Luke S.; Williamson, Philip T. F.; Barrantes, Francisco Jose; A mirror code for protein-cholesterol interactions in the two leaflets of biological membranes; Nature Publishing Group; Scientific Reports; 6; 2-2016; 1-14; 21907
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