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Updated: Aug 20, 2025
09:49
Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
Published on: April 2, 2015
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A diminished hydrophobic effect inside the GroEL/ES cavity contributes to protein substrate destabilization
Ilia Korobko1, Robin Benjamin Eberle1, Mousam Roy1
1Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Summary
Protein stability is reduced in confined biological compartments like the GroEL/ES chaperonin cage. This occurs due to a weakened hydrophobic effect caused by ordered water molecules, promoting protein unfolding.
Area of Science:
- Thermodynamics of protein folding
- Biophysical chemistry
- Molecular biology
Background:
- Confining compartments are common in biology, yet their impact on protein folding thermodynamics is understudied.
- Previous work showed reduced protein stability within the GroEL/ES chaperonin cage, but the cause was unknown.
Purpose of the Study:
- To elucidate the thermodynamic basis for reduced protein stability within the GroEL/ES chaperonin cage.
- To investigate the role of the hydrophobic effect and water ordering in protein encapsulation.
Main Methods:
- Experimental studies on protein folding thermodynamics.
- Analysis of protein stability in bulk solution versus the GroEL/ES cavity.
- Investigation of water ordering within the chaperonin cavity.
Main Results:
- Protein stability in the GroEL/ES cage is significantly reduced (>5 kcal mol-1) compared to bulk solution.
- This destabilization is partly due to a diminished hydrophobic effect within the GroEL/ES cavity.
- Water ordering between the cavity and protein surfaces likely causes the reduced hydrophobic effect.
Conclusions:
- Encapsulated proteins may undergo cold denaturation-like unfolding promoted by ordered water molecules.
- Findings support the iterative annealing mechanism of GroEL/ES chaperonin action.
- The thermodynamics of protein folding in confined biological environments are significantly altered.
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