Comparative analysis of GPCR crystal structures

Photochem Photobiol. 2009 Mar-Apr;85(2):425-30. doi: 10.1111/j.1751-1097.2008.00516.x. Epub 2009 Jan 19.

Abstract

The phototransduction cascade is perhaps the best understood model system for G protein-coupled receptor (GPCR) signaling. Phototransduction links the absorption of a single photon of light to a decrease in cytosolic cGMP. Depletion of the cGMP pool induces closure of cGMP-gated cation channels resulting in the hyperpolarization of photoreceptor cells and consequently a neuronal response. Many biochemical and both low- and high-resolution structural approaches have been utilized to increase our understanding of rhodopsin, the key molecule of this signaling cascade. Rhodopsin, a member of the GPCR or seven-transmembrane spanning receptor superfamily, is composed of a chromophore, 11-cis-retinal that is covalently bound by a protonated Schiff base linkage to the apo-protein opsin at Lys(296) (in bovine opsin). Upon absorption of a photon, isomerization of the chromophore to an all-trans-retinylidene conformation induces changes in the rhodopsin structure, ultimately converting it from an inactive to an activated state. This state allows it to activate the heterotrimeric G protein, transducin, by triggering nucleotide exchange. To fully understand the structural and functional aspects of rhodopsin it is necessary to critically examine crystal structures of its different photointermediates. In this review we summarize recent progress on the structure and activation of rhodopsin in the context of other GPCR structures.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Crystallization
  • Crystallography, X-Ray*
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Receptors, G-Protein-Coupled