Structural Plasticity in Remodeled Protein-Protein Interface

• Published in: Science (American Association for the Advancement of Science) Vol. 278; no. 5340; pp. 1125 - 1128
• Main Authors: Atwell, Shane, Ultsch, Mark, De Vos, Abraham M., Wells, James A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 07-11-1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Analytical, structural and metabolic biochemistry; Atoms; Bacteriophages; Binding and carrier proteins; Biochemistry; Biological and medical sciences; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Colors; Crystallography, X-Ray; Data collection; Fundamental and applied biological sciences. Psychology; Hormone receptors; Hormones; Human Growth Hormone - chemistry; Human Growth Hormone - genetics; Human Growth Hormone - metabolism; Humans; Hydrogen Bonding; Hydrogen bonds; Libraries; Models, Molecular; Mutagenesis; Mutation; Peptide Library; Physiological aspects; Protein Binding; Protein Conformation; Proteins; Receptors; Renovations; Somatotropin; Somatotropin receptors; Human; Protein hormone; Molecular evolution; Adenohypophyseal hormone; Molecular structure; STH; X ray spectrum; Molecular interaction; Molecular complex; Mutation; Coevolution; Hormonal receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.278.5340.1125

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 apentamutant of hGH by phage display that fills the cavity and largely restores binding affinity. A 2.1 $\angst $ 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.