RT Journal Article
SR Electronic
T1 Structural Plasticity in a Remodeled Protein-Protein Interface
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1125
OP 1128
DO 10.1126/science.278.5340.1125
VO 278
IS 5340
A1 Atwell, Shane
A1 Ultsch, Mark
A1 De Vos, Abraham M.
A1 Wells, James A.
YR 1997
UL http://science.sciencemag.org/content/278/5340/1125.abstract
AB Remodeling of the interface between human growth hormone (hGH) and the extracellular domain of its receptor was studied by deleting a critical tryptophan residue (at position 104) in the receptor, creating a large cavity, and selecting a pentamutant of hGH by phage display that fills the cavity and largely restores binding affinity. A 2.1 Å resolution x-ray structure of the mutant complex showed that the receptor cavity was filled by selected hydrophobic mutations of hGH. Large structural rearrangements occurred in the interface at sites that were distant from the mutations. Such plasticity may be a means for protein-protein interfaces to adapt to mutations as they coevolve.