The x-ray crystal structure of the complex between human growth hormon
e (hGH) and the extracellular domain of its first bound receptor (hGHb
p) shows that about 30 side chains from each protein make contact. Ind
ividual replacement of contact residues in the hGHbp with alanine show
ed that a central hydrophobic region, dominated by two tryptophan resi
dues, accounts for more than three-quarters of the binding free energy
. This ''functional epitope'' is surrounded by less important contact
residues that are generally hydrophilic and partially hydrated, so tha
t the interface resembles a cross section through a globular protein.
The functionally important residues on the hGHbp directly contact thos
e on hGH. Thus, only a small and complementary set of contact residues
maintains binding affinity, a property that may be general to protein
-protein interfaces.