G protein-coupled receptor activation: analysis of a highly constrained, "straitjacketed" rhodopsin

Biochemistry. 2000 Jul 11;39(27):7938-42. doi: 10.1021/bi000771f.

Abstract

G protein-coupled receptor (GPCR) activation is generally assumed to result in a significant structural rearrangement of the receptor, presumably involving the rigid body movement of transmembrane helices. We have investigated the activation of the GPCR rhodopsin by the construction and analysis of a mutant which contains a total of four disulfide bonds connecting the cytoplasmic ends of helices 1 and 7, and 3 and 5, and the extracellular ends of helices 3 and 4, and 5 and 6. Despite the constraints imposed by four disulfides, this "straitjacketed" receptor retains the ability to activate the G protein transducin and, therefore, provides insight into the molecular mechanism of the initial step in signal transduction of this important class of receptors.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • GTP-Binding Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Rhodopsin / chemistry
  • Rhodopsin / genetics
  • Rhodopsin / metabolism*

Substances

  • Receptors, Cell Surface
  • Rhodopsin
  • GTP-Binding Proteins