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Local conformational fluctuations can modulate the coupling between proton binding and global structural transitions
Steven T Whitten1, Bertrand García-Moreno E, Vincent J Hilser
1Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Summary
Local protein fluctuations significantly impact ligand binding and structural changes. Understanding these dynamics is key to explaining complex biological processes like allostery and cooperativity.
Area of Science:
- Biophysics
- Structural Biology
- Protein Dynamics
Background:
- Local conformational fluctuations in proteins influence their function.
- The interplay between ligand binding and protein structure is crucial for biological regulation.
Purpose of the Study:
- To quantitatively assess how proton binding affects the conformational ensemble of staphylococcal nuclease.
- To elucidate the role of local fluctuations in modulating ligand-binding affinity and cooperativity.
Main Methods:
- Analysis of acid unfolding and proton-binding data.
- Application of an ensemble-based protein model.
- Quantitative monitoring of microstate population distributions.
Main Results:
- Local fluctuations effectively modulate ligand-binding affinities.
- These fluctuations are key determinants of cooperativity in ligand-driven transitions.
- Local unfolding processes thermodynamically represent these fluctuations.
Conclusions:
- An ensemble-based protein description quantitatively links local fluctuations, ligand binding, and global transitions.
- Understanding protein conformation, energy, and dynamics is essential for mechanistic insights.
- This framework is vital for comprehending allostery, cooperativity, and macromolecular regulation.