STRUCTURAL PLASTICITY IN A REMODELED PROTEIN-PROTEIN INTERFACE

Remodeling of the interface between human growth hormone (hGH) and the extracellular domain of its receptor was studied by deleting a critic al tryptophan residue (at position 104) in the receptor, creating a la rge cavity, and selecting a pentamutant of hGH by phage display that f ills the cavity and largely restores binding affinity. A 2.1 Angstrom resolution x-ray structure of the mutant complex showed that the recep tor cavity was filled by selected hydrophobic mutations of hGH. Large structural rearrangements occurred in the inter face at sites that wer e distant from the mutations. Such plasticity may be a means for prote in-protein interfaces to adapt to mutations as they coevolve.