Early steps of the intramolecular signal transduction in rhodopsin explored by molecular dynamics simulations.
Details
Serval ID
serval:BIB_EF97A568A73D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Early steps of the intramolecular signal transduction in rhodopsin explored by molecular dynamics simulations.
Journal
Biochemistry
ISSN
0006-2960 (Print)
ISSN-L
0006-2960
Publication state
Published
Issued date
2002
Peer-reviewed
Oui
Volume
41
Number
35
Pages
10799-10809
Language
english
Abstract
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.
Keywords
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
Pubmed
Web of science
Create date
30/10/2015 9:56
Last modification date
20/08/2019 17:17