How a small change in retinal leads to G-protein activation: Initial events suggested by molecular dynamics calculations

Paul S. Crozier, Mark J. Stevens, Thomas B Woolf

Research output: Contribution to journalArticle

Abstract

Rhodopsin is the prototypical G-protein coupled receptor, coupling light activation with high efficiency to signaling molecules. The dark-state X-ray structures of the protein provide a starting point for consideration of the relaxation from initial light activation to conformational changes that may lead to signaling. In this study we create an energetically unstable retinal in the light activated state and then use molecular dynamics simulations to examine the types of compensation, relaxation, and conformational changes that occur following the cis-trans light activation. The results suggest that changes occur throughout the protein, with changes in the orientation of Helices 5 and 6, a closer interaction between Ala 169 on Helix 4 and retinal, and a shift in the Schiff base counterion that also reflects changes in. sidechain interactions with the retinal. Taken together, the simulation is suggestive of the types of changes that lead from local conformational change to light-activated signaling in this prototypical system.

Original languageEnglish (US)
Pages (from-to)559-574
Number of pages16
JournalProteins
Volume66
Issue number3
DOIs
StatePublished - Feb 15 2007

Fingerprint

Molecular Dynamics Simulation
GTP-Binding Proteins
Molecular dynamics
Chemical activation
Light
Rhodopsin
Schiff Bases
G-Protein-Coupled Receptors
Proteins
X-Rays
X rays
Molecules
Computer simulation

Keywords

  • G-protein coupled receptors
  • Membrane protein
  • Photoisomerization
  • Rhodopsin
  • Simulation

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

How a small change in retinal leads to G-protein activation : Initial events suggested by molecular dynamics calculations. / Crozier, Paul S.; Stevens, Mark J.; Woolf, Thomas B.

In: Proteins, Vol. 66, No. 3, 15.02.2007, p. 559-574.

Research output: Contribution to journalArticle

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