A mirror code for protein cholesterol interactions in the two leaflets of biological membranes
Abstract: 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 recepto...
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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Nature Research
2019
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/8684 |
| Aporte de: |
| id |
I33-R139123456789-8684 |
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| record_format |
dspace |
| institution |
Universidad Católica Argentina |
| institution_str |
I-33 |
| repository_str |
R-139 |
| collection |
Repositorio Institucional de la Universidad Católica Argentina (UCA) |
| language |
Inglés |
| topic |
MEDICINA COLESTEROL PROTEINAS NEUROTRANSMISORES |
| spellingShingle |
MEDICINA COLESTEROL PROTEINAS NEUROTRANSMISORES Fantini, Jacques Di Scala, Coralie Evans, Luke S. Williamson, Philip, T. F. Barrantes, Francisco José A mirror code for protein cholesterol interactions in the two leaflets of biological membranes |
| topic_facet |
MEDICINA COLESTEROL PROTEINAS NEUROTRANSMISORES |
| description |
Abstract: 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. |
| format |
Artículo |
| author |
Fantini, Jacques Di Scala, Coralie Evans, Luke S. Williamson, Philip, T. F. Barrantes, Francisco José |
| author_facet |
Fantini, Jacques Di Scala, Coralie Evans, Luke S. Williamson, Philip, T. F. Barrantes, Francisco José |
| author_sort |
Fantini, Jacques |
| title |
A mirror code for protein cholesterol interactions in the two leaflets of biological membranes |
| title_short |
A mirror code for protein cholesterol interactions in the two leaflets of biological membranes |
| title_full |
A mirror code for protein cholesterol interactions in the two leaflets of biological membranes |
| title_fullStr |
A mirror code for protein cholesterol interactions in the two leaflets of biological membranes |
| title_full_unstemmed |
A mirror code for protein cholesterol interactions in the two leaflets of biological membranes |
| title_sort |
mirror code for protein cholesterol interactions in the two leaflets of biological membranes |
| publisher |
Nature Research |
| publishDate |
2019 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/8684 |
| work_keys_str_mv |
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Repositorios |
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