Crystal structure of opsin in its G-protein-interacting conformation

Nature. 2008 Sep 25;455(7212):497-502. doi: 10.1038/nature07330.

Abstract

Opsin, the ligand-free form of the G-protein-coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G-protein-binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein-the carboxy terminus of the alpha-subunit (GalphaCT)-stabilizes Ops*. Here we present the 3.2 A crystal structure of the bovine Ops*-GalphaCT peptide complex. GalphaCT binds to a site in opsin that is opened by an outward tilt of transmembrane helix (TM) 6, a pairing of TM5 and TM6, and a restructured TM7-helix 8 kink. Contacts along the inner surface of TM5 and TM6 induce an alpha-helical conformation in GalphaCT with a C-terminal reverse turn. Main-chain carbonyl groups in the reverse turn constitute the centre of a hydrogen-bonded network, which links the two receptor regions containing the conserved E(D)RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops*-GalphaCT structure and known conformational changes in Galpha, we discuss signal transfer from the receptor to the G protein nucleotide-binding site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Arginine / chemistry
  • Arginine / metabolism
  • Binding Sites
  • Cattle
  • Conserved Sequence
  • Crystallization
  • Crystallography, X-Ray
  • GTP-Binding Protein alpha Subunits / chemistry*
  • GTP-Binding Protein alpha Subunits / metabolism*
  • Models, Biological
  • Models, Molecular
  • Protein Conformation
  • Regeneration
  • Retinaldehyde / chemistry
  • Retinaldehyde / metabolism
  • Rhodopsin / chemistry
  • Rod Opsins / chemistry*
  • Rod Opsins / metabolism*
  • Signal Transduction

Substances

  • GTP-Binding Protein alpha Subunits
  • Rod Opsins
  • Rhodopsin
  • Arginine
  • Retinaldehyde

Associated data

  • PDB/3DQB