A HOT-SPOT OF BINDING-ENERGY IN A HORMONE-RECEPTOR INTERFACE

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.