The incorporation of cysteine residues into membrane receptors by mutagenes
is has enabled the development of engineered proteins. Chemical modificatio
n of the mutant receptor using a wide range of biochemical and biophysical
probes has facilitated functional studies of ligand-receptor interactions.
In particular, the substituted-cysteine accessibility method (SCAM) represe
nts a successful example of how to probe transmembrane receptor domains aft
er chemical modification of the mutants with sulfydryl-reacting molecules.
We propose an extension of this methodology using site-specific affinity pr
obes that react with cysteine mutants to gain reliable structural informati
on on the binding of a ligand in its receptor site.