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The α-factor receptor of the yeast Saccharomyces cerevisiae is a member of the superfamily of G protein-coupled receptors that mediate signal transduction in response to sensory and chemical stimuli. All members of this superfamily contain seven predicted transmembrane segments. We have created a series of genes encoding α-factor receptors with amino- or carboxyl-terminal truncations at each of the loop regions connecting transmembrane segments. Split receptors containing a discontinuity in the peptide backbone were synthesized by coexpressing pairs of truncated receptor fragments in yeast. Complementary pairs of fragments split at sites within each of the cytoplasmic and extracellular loops were capable of assembling and transducing a signal in response to α-factor binding. One pair of noncomplementary fragments containing a deletion in the second intracellular loop of the receptor also yielded a …