Evolutionarily conserved Galphabetagamma binding surfaces support a model of the G protein-receptor complex

Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7507-11. doi: 10.1073/pnas.93.15.7507.


The pivotal role of G proteins in sensory, hormonal, inflammatory, and proliferative responses has provoked intense interest in understanding how they interact with their receptors and effectors. Nonetheless, the locations of the receptors and effector binding sites remain poorly characterized, although nearly complete structures of the alphabetagamma heterotrimeric complex are available. Here we apply evolutionary trace (ET) analysis [Lichtarge, O., Bourne, H. R. & Cohen, F. E. (1996) J. Mol. Biol. 257, 342-358] to propose plausible locations for these sites. On each subunit, ET identifies evolutionarily selected surfaces composed of residues that do not vary within functional subgroups and that form spatial clusters. Four clusters correctly identify subunit interfaces, and additional clusters on Galpha point to likely receptor or effector binding sites. Our results implicate the conformationally variable region of Galpha in an effector binding role. Furthermore the range of predicted interactions between the receptor and Galphabetagamma, is sufficiently limited that we can build a low resolution and testable model of the receptor-G protein complex.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Biological Evolution*
  • Conserved Sequence
  • Databases, Factual
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Macromolecular Substances
  • Models, Molecular
  • Protein Conformation*
  • Protein Structure, Secondary
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / genetics


  • Macromolecular Substances
  • Receptors, Cell Surface
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP-Binding Proteins