G protein coupled receptor interactions with cholesterol deep in the membrane
G protein coupled receptor interactions with cholesterol deep in the membrane
G-protein coupled receptors (GPCRs) are located in membranes rich in cholesterol. The membrane spanning surfaces of GPCRs contain exposed backbone carbonyl groups and residue side chains potentially capable of forming hydrogen bonds to cholesterol molecules buried deep within the hydrophobic core of the lipid bilayer. Coarse-grained
molecular dynamics (CGMD) simulations allow the observation
of GPCRs in cholesterol-containing lipid bilayersfor long times (50 ?s), sufficient to ensure equilibration of the
system. We have detected a number of deep cholesterol binding sites on ?2adrenergic and A2Aadenosine receptors, and shown changes in these sites on agonist binding. The requirements for binding are modest, just a potential hydrogen bond partner close to a cleft or hole in the surface. This makes it likely that similar binding sites for cholesterol will exist on other classes of membrane protein.
268-281
Genheden, Samuel
cc461200-48bd-411b-8424-23dfef65cc86
Essex, Jonathan
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Lee, Anthony
0891914c-e0e2-4ee1-b43e-1b70eb072d8e
February 2017
Genheden, Samuel
cc461200-48bd-411b-8424-23dfef65cc86
Essex, Jonathan
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Lee, Anthony
0891914c-e0e2-4ee1-b43e-1b70eb072d8e
Genheden, Samuel, Essex, Jonathan and Lee, Anthony
(2017)
G protein coupled receptor interactions with cholesterol deep in the membrane.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1859 (2), .
(doi:10.1016/j.bbamem.2016.12.001).
Abstract
G-protein coupled receptors (GPCRs) are located in membranes rich in cholesterol. The membrane spanning surfaces of GPCRs contain exposed backbone carbonyl groups and residue side chains potentially capable of forming hydrogen bonds to cholesterol molecules buried deep within the hydrophobic core of the lipid bilayer. Coarse-grained
molecular dynamics (CGMD) simulations allow the observation
of GPCRs in cholesterol-containing lipid bilayersfor long times (50 ?s), sufficient to ensure equilibration of the
system. We have detected a number of deep cholesterol binding sites on ?2adrenergic and A2Aadenosine receptors, and shown changes in these sites on agonist binding. The requirements for binding are modest, just a potential hydrogen bond partner close to a cleft or hole in the surface. This makes it likely that similar binding sites for cholesterol will exist on other classes of membrane protein.
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Accepted/In Press date: 1 December 2016
e-pub ahead of print date: 3 December 2016
Published date: February 2017
Organisations:
Faculty of Natural and Environmental Sciences
Identifiers
Local EPrints ID: 403825
URI: http://eprints.soton.ac.uk/id/eprint/403825
ISSN: 0304-4165
PURE UUID: f2d42860-bf60-4219-b758-d13a02247171
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Date deposited: 13 Dec 2016 11:37
Last modified: 16 Mar 2024 02:45
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Author:
Samuel Genheden
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