Lipids Alter Rhodopsin Function via Ligand-like and Solvent-like Interactions.
Biophys J
; 114(2): 355-367, 2018 01 23.
Article
in En
| MEDLINE
| ID: mdl-29401433
ABSTRACT
Rhodopsin, a prototypical G protein-coupled receptor, is a membrane protein that can sense dim light. This highly effective photoreceptor is known to be sensitive to the composition of its lipidic environment, but the molecular mechanisms underlying this fine-tuned modulation of the receptor's function and structural stability are not fully understood. There are two competing hypotheses to explain how this occurs 1) lipid modulation occurs via solvent-like interactions, where lipid composition controls membrane properties like hydrophobic thickness, which in turn modulate the protein's conformational equilibrium; or 2) protein-lipid interactions are ligand-like, with specific hot spots and long-lived binding events. By analyzing an ensemble of all-atom molecular dynamics simulations of five different states of rhodopsin, we show that a local ordering effect takes place in the membrane upon receptor activation. Likewise, docosahexaenoic acid acyl tails and phosphatidylethanolamine headgroups behave like weak ligands, preferentially binding to the receptor in inactive-like conformations and inducing subtle but significant structural changes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphatidylethanolamines
/
Rhodopsin
/
Solvents
Limits:
Animals
Language:
En
Journal:
Biophys J
Year:
2018
Document type:
Article