Interfacial binding sites for cholesterol on G protein-coupled receptors
Interfacial binding sites for cholesterol on G protein-coupled receptors
A docking procedure is described that allows the transmembrane surface of a G protein-coupled receptor (GPCR) to be swept rapidly for potential binding sites for cholesterol at the bilayer interfaces on the two sides of the membrane. The procedure matches 89% of the cholesterols resolved in published GPCR crystal structures, when cholesterols likely to be crystal packing artifacts are excluded. Docking poses are shown to form distinct clusters on the protein surface, the clusters corresponding to “greasy hollows” between protein ridges. Docking poses depend on the angle of tilt of the GPCR in the surrounding lipid bilayer. It is suggested that thermal motion could alter the optimal binding pose for a cholesterol molecule, with the range of binding poses within a cluster providing a guide to the range of thermal motions likely for a cholesterol within a binding site.
1586-1597
Lee, Anthony G.
0891914c-e0e2-4ee1-b43e-1b70eb072d8e
7 May 2019
Lee, Anthony G.
0891914c-e0e2-4ee1-b43e-1b70eb072d8e
Lee, Anthony G.
(2019)
Interfacial binding sites for cholesterol on G protein-coupled receptors.
Biophysical Journal, 116 (9), .
(doi:10.1016/j.bpj.2019.03.025).
Abstract
A docking procedure is described that allows the transmembrane surface of a G protein-coupled receptor (GPCR) to be swept rapidly for potential binding sites for cholesterol at the bilayer interfaces on the two sides of the membrane. The procedure matches 89% of the cholesterols resolved in published GPCR crystal structures, when cholesterols likely to be crystal packing artifacts are excluded. Docking poses are shown to form distinct clusters on the protein surface, the clusters corresponding to “greasy hollows” between protein ridges. Docking poses depend on the angle of tilt of the GPCR in the surrounding lipid bilayer. It is suggested that thermal motion could alter the optimal binding pose for a cholesterol molecule, with the range of binding poses within a cluster providing a guide to the range of thermal motions likely for a cholesterol within a binding site.
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Accepted/In Press date: 25 March 2019
e-pub ahead of print date: 2 April 2019
Published date: 7 May 2019
Identifiers
Local EPrints ID: 430722
URI: http://eprints.soton.ac.uk/id/eprint/430722
ISSN: 0006-3495
PURE UUID: d8f9903a-7633-4191-8d8a-647e8654522e
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Date deposited: 09 May 2019 16:30
Last modified: 16 Mar 2024 01:45
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