Protein Engineering, Vol. 12, No. 12, 1087-1095,
December 1999
© 1999 Oxford University Press
A low resolution model for the interaction of G proteins with G protein-coupled receptors
Escola Paulista de Medicina, UNIFESP, Sao Paulo, Brazil and 1 BIOcomputing, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
A model is presented for the interaction between G proteins and G protein-coupled receptors. The model is based on the fact that this interaction shows little specificity and thus conserved parts of the G proteins have to interact with conserved parts of the receptors. These parts are a conserved negative residue in the G protein, a fully conserved arginine in the receptor and a series of residues that are not conserved but always hydrophobic like the hydrophobic side of the C-terminal helix of the G protein and the hydrophobic side of a helix in the C-terminal domain of the receptor. Other, mainly cytosolic, factors determine the specificity and regulation of this interaction. The relation between binding and activation will be shown. A large body of experimental evidence supports this model. Despite the fact that the model does not provide atomic resolution, it can be used to explain some experimental data that would otherwise seem inexplicable, and it suggests experiments for its falsification or verification.
Keywords: GPCR/G protein interaction/model
2 To whom correspondence should be addressed; email: Vriend{at}EMBL-Heidelberg.DE
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