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Bio-layer Interferometry for Measuring Kinetics of Protein-protein Interactions and Allosteric Ligand Effects
Published on: February 18, 2014
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Substrates Modulate Charge-Reorganization Allosteric Effects in Protein-Protein Association
Shirsendu Ghosh1, Koyel Banerjee-Ghosh1, Dorit Levy1
1Department of Chemical and Biological Physics, Weizmann Institute, Rehovot 76100, Israel.
The Journal of Physical Chemistry Letters
|March 12, 2021
Summary
Charge-Reorganization Allostery (CRA) is a newly observed phenomenon where charge shifts in proteins modulate function. This study shows CRA in enzyme-antibody interactions and how substrates like ATP significantly impact this allosteric effect.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Dynamics
Background:
- Allostery classically involves conformational changes distant from the active site.
- Recent findings suggest charge redistribution can also mediate allosteric effects.
- Antibody-mediated allostery, particularly Charge-Reorganization Allostery (CRA), is an emerging area of study.
Purpose of the Study:
- To investigate Charge-Reorganization Allostery (CRA) in the interaction between an enzyme and an antibody.
- To determine the impact of charged substrates on CRA.
- To elucidate the role of charge redistribution in protein function modulation.
Main Methods:
- Studied the association of polyhistidine-tagged phosphoglycerate kinase (PGK) with surface-immobilized anti-His antibodies.
- Quantified the Charge-Reorganization Allostery (CRA) effect.
- Assessed the modulation of CRA by PGK's nucleotide substrates, including ATP.
Main Results:
- A significant Charge-Reorganization Allostery (CRA) effect was observed during the enzyme-antibody association.
- Charged nucleotide substrates, such as ATP, substantially modulated CRA.
- ATP binding reduced CRA by over 50%, demonstrating substrate influence on allosteric charge effects.
Conclusions:
- Charge-Reorganization Allostery (CRA) is influenced by the binding of charged molecules to proteins.
- Charge redistribution plays a significant role in modulating protein function, extending beyond classical allosteric mechanisms.
- This study provides new insights into the mechanisms of allosteric regulation in protein-antibody interactions.
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