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Structural response to mutation at a protein-protein interface.

C K Vaughan1, A M Buckle, A R Fersht

  • 1MRC Centre for Protein Engineering, Hills Road, Cambridge, CB2 2QH, UK.

Journal of Molecular Biology
|March 5, 1999
PubMed
Summary
This summary is machine-generated.

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Mutating barnase-barstar complexes to remove specific interactions revealed local structural changes. Water molecules often filled the resulting gaps, mimicking deleted side-chains but complicating direct energy-structure correlations.

Area of Science:

  • Structural biology
  • Protein-protein interactions
  • Biochemistry

Background:

  • The barnase-barstar complex is a model system for studying protein-protein interactions and stability.
  • Understanding how mutations affect protein complex stability and structure is crucial for protein engineering and drug design.

Purpose of the Study:

  • To investigate the structural and energetic consequences of deleting specific interface interactions in the barnase-barstar complex.
  • To analyze the local structural response to mutations and the role of water molecules in stabilizing mutant complexes.

Main Methods:

  • Crystallization of three barnase-barstar double mutants, each designed to eliminate a distinct interface interaction (van der Waals, hydrogen bond, charge-charge).
  • X-ray crystallography to determine the structures of the wild-type and mutant complexes.

Related Experiment Videos

  • Analysis of structural changes, including main-chain and side-chain movements, and the formation of interfacial pockets/cavities.

    • Main Results:

    • Despite significant destabilization, mutations primarily caused local structural effects with minimal main-chain rearrangements.
    • Mutant complexes exhibited varied responses, forming either solvent-accessible pockets or isolated cavities at the interface.
    • Water molecules consistently occupied these interfacial voids, often re-establishing hydrogen bonds and mimicking the deleted side-chains.

    Conclusions:

    • The structural response to interface mutations is context-dependent and can be significantly influenced by the local environment.
    • Water molecules play a critical role in stabilizing mutant complexes by filling interfacial voids and mimicking lost interactions.
    • Correlating energetic and structural data remains challenging due to uncharacterized entropic contributions and entropy-enthalpy compensation.