Article: article from journal or magazin.
Early steps of the intramolecular signal transduction in rhodopsin explored by molecular dynamics simulations.
We present molecular dynamics simulations of bovine rhodopsin in a membrane mimetic environment based on the recently refined X-ray structure of the pigment. The interactions between the protonated Schiff base and the protein moiety are explored both with the chromophore in the dark-adapted 11-cis and in the photoisomerized all-trans form. Comparison of simulations with Glu181 in different protonation states strongly suggests that this loop residue located close to the 11-cis bond bears a negative charge. Restrained molecular dynamics simulations also provide evidence that the protein tightly confines the absolute conformation of the retinal around the C12-C13 bond to a positive helicity. 11-cis to all-trans isomerization leads to an internally strained chromophore, which relaxes after a few nanoseconds by a switching of the ionone ring to an essentially planar all-trans conformation. This structural transition of the retinal induces in turn significant conformational changes of the protein backbone, especially in helix VI. Our results suggest a possible molecular mechanism for the early steps of intramolecular signal transduction in a prototypical G-protein-coupled receptor.
Animals, Cattle, Computational Biology/methods, Computer Simulation, Crystallography, X-Ray, Glutamic Acid/chemistry, Hydrogen-Ion Concentration, Isomerism, Membrane Proteins/chemistry, Membrane Proteins/physiology, Models, Molecular, Molecular Mimicry, Protein Conformation, Protons, Retinaldehyde/chemistry, Retinoids/chemistry, Rhodopsin/chemistry, Rhodopsin/physiology, Signal Transduction, Software, Thermodynamics
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