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The steric trigger in rhodopsin activation

T Shieh1, M Han, T P Sakmar

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.

Journal of Molecular Biology
|June 13, 1997
PubMed
Summary
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Rhodopsin

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Vision Science

Background:

  • Rhodopsin, a G protein-coupled receptor, mediates dim light vision.
  • Its ligand, 11-cis retinal, covalently binds and changes from antagonist to agonist upon light absorption.
  • Structural homology exists with other G protein-coupled receptors.

Purpose of the Study:

  • To elucidate the activation mechanism of rhodopsin.
  • To understand the role of retinal isomerization in receptor activation.
  • To investigate the structural basis of retinal-binding site selectivity.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy of rhodopsin and bathorhodopsin.
  • Computational docking of retinal chromophores into protein models.

Related Experiment Videos

  • Site-directed mutagenesis studies of the retinal-binding site.
  • Main Results:

    • Structural constraints from NMR enabled chromophore docking into a low-resolution rhodopsin model.
    • A mechanism for light-induced rhodopsin activation involving retinal isomerization was proposed.
    • Mutagenesis revealed modifications to favor all-trans retinal binding.
    • A direct steric interaction between retinal and transmembrane helix 3 (Gly121 region) was identified.

    Conclusions:

    • Retinal isomerization and steric interactions drive rhodopsin activation.
    • Understanding rhodopsin structure-function provides insights into G protein-coupled receptor mechanisms.
    • Mutagenesis offers a route to engineer chromophore selectivity in visual pigments.