期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
卷 1818, 期 9, 页码 2228-2233出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2012.04.010
关键词
Neurotensin; GPCR; Cholesterol; Reconstitution; POPE; FRET
资金
- Medical Research Council (MRC) [G0900076]
- Engineering and Physical Sciences Research Council (EPSRC) [EP/D048559/1]
- BBSRC [BB/H000321/1] Funding Source: UKRI
- EPSRC [EP/D048559/1] Funding Source: UKRI
- MRC [G0900076] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H000321/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/D048559/1] Funding Source: researchfish
- Medical Research Council [G0900076] Funding Source: researchfish
Understanding the role of specific bilayer components in controlling the function of G-protein coupled receptors (GPCRs) will be a key factor in the development of novel pharmaceuticals. Cholesterol-dependence in particular has become an area of keen interest with respect to GPCR function; not least since the 2.6 angstrom crystal structure of the in beta 2 adrenergic receptor revealed a putative cholesterol binding motif conserved throughout class-A GPCRs. Furthermore, experimental evidence for cholesterol-dependent GPCR function has been demonstrated in a limited number of cases. This modulation of receptor function has been attributed to both direct interactions between cholesterol and receptor, and indirect effects caused by the influence of cholesterol on bilayer order and lateral pressure. Despite the widespread occurrence of cholesterol binding motifs, available experimental data on the functional involvement of cholesterol on GPCRs are currently limited to a small number of receptors. Here we investigate the role of cholesterol in the function of the neurotensin receptor 1 (NTS1) a class-A GPCR. Specifically we show how cholesterol, and the analogue cholesteryl hemisuccinate, influence activity, stability, and oligomerisation of both purified and reconstituted NTS1. The results caution against using such motifs as indicators of cholesterol-dependent GPCR activity. (C) 2012 Elsevier B.V. All rights reserved.
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