Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors
Abstract: Cholesterol is a ubiquitous neutral lipid, which finely tunes the activity of a wide range of membrane proteins, including neurotransmitter and hormone receptors and ion channels. Given the scarcity of available X-ray crystallographic structures and the even fewer in which cholesterol sites have been directly visualized, application of in silico computational methods remains a valid alternative for the detection and thermodynamic characterization of cholesterol-specific sites in functionally important membrane proteins. The membrane-embedded segments of the paradigm neurotransmitter receptor for acetylcholine display a series of cholesterol consensus domains (which we have coined “CARC”). The CARC motif exhibits a preference for the outer membrane leaflet and its mirror motif, CRAC, for the inner one. Some membrane proteins possess the double CARC–CRAC sequences within the same transmembrane domain. In addition to in silico molecular modeling, the affinity, concentration dependence, and specificity of the cholesterol-recognition motif–protein interaction have recently found experimental validation in other biophysical approaches like monolayer techniques and nuclear magnetic resonance spectroscopy. From the combined studies, it becomes apparent that the CARC motif is now more firmly established as a high-affinity cholesterol-binding domain for membrane-bound receptors and remarkably conserved along phylogenetic evolution.
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oai:ucacris:123456789-14602020-08-19T00:19:08Z Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors Di Scala, Coralie Baier, Carlos J. Evans, Luke S. Williamson, Philip, T. F. Fantini, Jacques Barrantes, Francisco José COLESTEROL PROTEINAS NEUROTRANSMISORES Abstract: Cholesterol is a ubiquitous neutral lipid, which finely tunes the activity of a wide range of membrane proteins, including neurotransmitter and hormone receptors and ion channels. Given the scarcity of available X-ray crystallographic structures and the even fewer in which cholesterol sites have been directly visualized, application of in silico computational methods remains a valid alternative for the detection and thermodynamic characterization of cholesterol-specific sites in functionally important membrane proteins. The membrane-embedded segments of the paradigm neurotransmitter receptor for acetylcholine display a series of cholesterol consensus domains (which we have coined “CARC”). The CARC motif exhibits a preference for the outer membrane leaflet and its mirror motif, CRAC, for the inner one. Some membrane proteins possess the double CARC–CRAC sequences within the same transmembrane domain. In addition to in silico molecular modeling, the affinity, concentration dependence, and specificity of the cholesterol-recognition motif–protein interaction have recently found experimental validation in other biophysical approaches like monolayer techniques and nuclear magnetic resonance spectroscopy. From the combined studies, it becomes apparent that the CARC motif is now more firmly established as a high-affinity cholesterol-binding domain for membrane-bound receptors and remarkably conserved along phylogenetic evolution. 2019-05-02T13:56:19Z 2019-05-02T13:56:19Z 2017 Artículo Di Scala, C., et al. Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors [en línea]. Postprint del artículo publicado en Current Topics in Membranes. 2017, 80. doi:10.1016/bs.ctm.2017.05.001. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/1460 1063-5823 https://repositorio.uca.edu.ar/handle/123456789/1460 10.1016/bs.ctm.2017.05.001 eng spa Acceso Abierto. 1 año de embargo https://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier Postprint del artículo publicado en Current Topics in Membranes 2017, 80 1063-5823 |
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COLESTEROL PROTEINAS NEUROTRANSMISORES COLESTEROL PROTEINAS NEUROTRANSMISORES Di Scala, Coralie Baier, Carlos J. Evans, Luke S. Williamson, Philip, T. F. Fantini, Jacques Barrantes, Francisco José Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors |
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Abstract: Cholesterol is a ubiquitous neutral lipid, which finely tunes the activity of a wide range of membrane proteins, including neurotransmitter and hormone receptors and ion channels. Given the scarcity of available X-ray crystallographic structures and the even fewer in which cholesterol sites have been directly visualized, application of in silico computational methods remains a valid alternative for the detection and thermodynamic characterization of cholesterol-specific sites in functionally important membrane proteins. The membrane-embedded segments of the paradigm neurotransmitter receptor for acetylcholine display a series of cholesterol consensus domains (which we have coined “CARC”). The CARC motif exhibits a preference for the outer membrane leaflet and its mirror motif, CRAC, for the inner one. Some membrane proteins possess the double CARC–CRAC sequences within the same transmembrane domain. In addition to in silico molecular modeling, the affinity, concentration dependence, and specificity of the cholesterol-recognition motif–protein interaction have recently found experimental validation in other biophysical approaches like monolayer techniques and nuclear magnetic resonance spectroscopy. From the combined studies, it becomes apparent that the CARC motif is now more firmly established as a high-affinity cholesterol-binding domain for membrane-bound receptors and remarkably conserved along phylogenetic evolution. |
format |
Artículo |
topic_facet |
COLESTEROL PROTEINAS NEUROTRANSMISORES |
author |
Di Scala, Coralie Baier, Carlos J. Evans, Luke S. Williamson, Philip, T. F. Fantini, Jacques Barrantes, Francisco José |
author_facet |
Di Scala, Coralie Baier, Carlos J. Evans, Luke S. Williamson, Philip, T. F. Fantini, Jacques Barrantes, Francisco José |
author_sort |
Di Scala, Coralie |
title |
Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors |
title_short |
Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors |
title_full |
Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors |
title_fullStr |
Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors |
title_full_unstemmed |
Relevance of CARC and CRAC cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors |
title_sort |
relevance of carc and crac cholesterol-recognition motifs in the nicotinic azcetylcholine receptor and other membrane-bound receptors |
publisher |
Elsevier |
publishDate |
2017 |
url |
https://repositorio.uca.edu.ar/handle/123456789/1460 |
work_keys_str_mv |
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