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Related Experiment Videos

Structural plasticity in a remodeled protein-protein interface

S Atwell1, M Ultsch, A M De Vos

  • 1Department of Protein Engineering, Genentech, Incorporated, 460 Point San Bruno Boulevard, South San Francisco, CA 94080, USA.

Science (New York, N.Y.)
|November 14, 1997
PubMed
Summary
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Researchers studied how human growth hormone (hGH) and its receptor interact. They found that protein interfaces can undergo significant structural changes to adapt to mutations, a process crucial for co-evolution.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Evolution

Background:

  • The interaction between human growth hormone (hGH) and its receptor is vital for biological signaling.
  • Understanding protein-protein interfaces is key to deciphering molecular recognition and function.

Purpose of the Study:

  • To investigate the structural plasticity of the hGH-receptor interface.
  • To explore how mutations at the interface affect binding affinity and structural dynamics.

Main Methods:

  • Site-directed mutagenesis to remove a key tryptophan residue in the receptor.
  • Phage display to select for hGH variants that bind the modified receptor.
  • X-ray crystallography to determine the structure of the mutant complex at 2.1 Å resolution.

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Main Results:

  • A pentamutant hGH variant was identified that effectively filled a cavity created in the receptor.
  • The selected mutations in hGH were predominantly hydrophobic, interacting with the receptor cavity.
  • Significant, long-range structural rearrangements were observed at the protein-protein interface distant from the introduced mutations.

Conclusions:

  • Protein interfaces exhibit remarkable plasticity, allowing adaptation to mutations.
  • This adaptability may be a fundamental mechanism enabling the co-evolution of interacting proteins.
  • The findings provide insights into the dynamic nature of protein-ligand interactions.