Role of aggregation in rhodopsin signal transduction

Biochemistry. 2010 Jun 15;49(23):4827-32. doi: 10.1021/bi100478j.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cell Membrane / physiology
  • Cross-Linking Reagents / metabolism
  • Dimerization
  • Evolution, Molecular
  • Intracellular Space / metabolism
  • Intracellular Space / physiology
  • Microscopy, Atomic Force
  • Molecular Dynamics Simulation
  • Multigene Family
  • Protein Conformation
  • Protein Subunits / metabolism
  • Protein Subunits / physiology
  • Receptor Cross-Talk / physiology
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D2 / physiology
  • Rhodopsin / chemistry
  • Rhodopsin / metabolism
  • Rhodopsin / physiology*
  • Signal Transduction / physiology*

Substances

  • Cross-Linking Reagents
  • Protein Subunits
  • Receptors, Dopamine D2
  • Rhodopsin