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Interfacial binding sites for cholesterol on G protein-coupled receptors

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.

0006-3495
1586-1597
Lee, Anthony G.
0891914c-e0e2-4ee1-b43e-1b70eb072d8e
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), 1586-1597. (doi:10.1016/j.bpj.2019.03.025).

Record type: Article

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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More information

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

Catalogue record

Date deposited: 09 May 2019 16:30
Last modified: 14 Sep 2021 16:46

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