Role of aggregation in rhodopsin signal transduction.
Many G protein-coupled receptors (GPCRs) are known to form dimers or even oligomers, and these aggregated states have been proposed as functional units responsible for signal transduction and G protein activation. However, the nature of their involvement has remained elusive. Here, we have investigated the role of aggregation in the signal transduction for dimeric forms of the prototypical GPCR rhodopsin using molecular dynamics simulations. The early steps after photoexcitation are characterized by a tandem mechanism in which one monomer is responsible for light detection while the other serves as the G protein activation site. Dimerization ensures efficient cross-talk between the two units within a few tens of nanoseconds following photoexcitation. This interface-mediated pathway suggests oligomerization-aided signal transduction as a crucial biological strategy to enhance activation efficiency across the entire family of GPCRs.
Neri
Marilisa
M
Laboratory of Computational Chemistry, Ecole Polytechnique Federale de Lausanne, Lausanne CH-1015, Switzerland.
Vanni
Stefano
S
Tavernelli
Ivano
I
Rothlisberger
Ursula
U
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D003432:Cross-Linking Reagents / Q000378:metabolism; D019281:Dimerization; D019143:Evolution, Molecular; D042541:Intracellular Space / Q000378:metabolism / Q000502:physiology; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D005810:Multigene Family; D011487:Protein Conformation; D021122:Protein Subunits / Q000378:metabolism / Q000502:physiology; D020239:Receptor Cross-Talk / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism / Q000502:physiology; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D003432:Cross-Linking Reagents; D021122:Protein Subunits; D017448:Receptors, Dopamine D2; D012243:Rhodopsin