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.
Röhrig
Ute F
UF
Laboratory of Inorganic Chemistry, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
Guidoni
Leonardo
L
Rothlisberger
Ursula
U
D000818:Animals; D002417:Cattle; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D018698:Glutamic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D018716:Molecular Mimicry; D011487:Protein Conformation; D011522:Protons; D012172:Retinaldehyde / Q000737:chemistry; D012176:Retinoids / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry* / Q000502:physiology*; D015398:Signal Transduction; D012984:Software; D013816:Thermodynamics
D008565:Membrane Proteins; D011522:Protons; D012176:Retinoids; C121835:retinylidene chromophore; D018698:Glutamic Acid; D012243:Rhodopsin; D012172:Retinaldehyde