Rhodopsin controls a conformational switch on the transducin gamma subunit

Structure. 2003 Apr;11(4):367-73. doi: 10.1016/s0969-2126(03)00045-5.

Abstract

Rhodopsin, a prototypical G protein-coupled receptor, catalyzes the activation of a heterotrimeric G protein, transducin, to initiate a visual signaling cascade in photoreceptor cells. The betagamma subunit complex, especially the C-terminal domain of the transducin gamma subunit, Gtgamma(60-71)farnesyl, plays a pivotal role in allosteric regulation of nucleotide exchange on the transducin alpha subunit by light-activated rhodopsin. We report that this domain is unstructured in the presence of an inactive receptor but forms an amphipathic helix upon rhodopsin activation. A K65E/E66K charge reversal mutant of the gamma subunit has diminished interactions with the receptor and fails to adopt the helical conformation. The identification of this conformational switch provides a mechanism for active GPCR utilization of the betagamma complex in signal transfer to G proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Heterotrimeric GTP-Binding Proteins / chemistry
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding
  • Protein Prenylation
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rhodopsin / chemistry*
  • Rhodopsin / genetics
  • Rhodopsin / metabolism*
  • Sequence Alignment
  • Signal Transduction / physiology
  • Transducin / chemistry*
  • Transducin / genetics
  • Transducin / metabolism*

Substances

  • Macromolecular Substances
  • Peptides
  • Protein Subunits
  • Rhodopsin
  • Heterotrimeric GTP-Binding Proteins
  • Transducin

Associated data

  • PDB/1MF6