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Related Experiment Videos

Co-operative interactions during protein folding.

A Horovitz1, A R Fersht

  • 1MRC Unit for Protein Function and Design, University of Cambridge, U.K.

Journal of Molecular Biology
|April 5, 1992
PubMed
Summary
This summary is machine-generated.

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Protein engineering experiments reveal synergistic interactions in proteins by measuring interaction energy (delta nGint) at increasing residue orders. These synergistic effects are significant in barnase

Area of Science:

  • Protein engineering
  • Biophysics
  • Structural biology

Background:

  • Measuring co-operativity in protein interactions is crucial for understanding protein folding and function.
  • Existing methods often focus on pairwise interactions, potentially missing higher-order synergistic effects.
  • Protein engineering offers a powerful approach to dissecting complex molecular interactions.

Purpose of the Study:

  • To develop and validate a theoretical framework for measuring multi-residue interaction synergy (delta nGint) in proteins.
  • To apply this framework to quantify synergistic interactions in the barnase protein during refolding.
  • To investigate the changes in co-operativity between the folded state and the transition state of unfolding.

Main Methods:

  • Development of a theoretical procedure to analyze increasing orders of synergy (delta nGint) using multi-dimensional mutant space.

Related Experiment Videos

  • Experimental measurement of interaction energies using double-mutant cycles and extensions to triple-mutant cubes.
  • Application to a salt-linked triad (Asp8, Asp12, Arg110) in barnase, mutated to alanine.

    • Main Results:

    • The delta 3Gint value in folded barnase indicates significant synergy (0.77 kcal mol-1) beyond pairwise interactions.
    • Synergistic interactions remain significant in the transition state for unfolding (0.60 kcal mol-1) and the folding intermediate (0.60 kcal mol-1).
    • A decrease in co-operativity (0.17 kcal mol-1) was observed between the folded and transition states, suggesting structural loosening during initial unfolding.

    Conclusions:

    • Synergistic interactions are integral to the stability of barnase across different conformational states, including folded, transition, and intermediate states.
    • The developed delta nGint method effectively quantifies higher-order synergistic effects in protein interactions.
    • The findings provide insights into the dynamics of protein folding and unfolding, highlighting the role of co-operativity.