Substrates modulate charge-reorganization allosteric effects in protein-protein association

TL;DR

This study reveals how substrate charge influences allosteric effects in protein-protein interactions, specifically showing that nucleotide binding can significantly modulate charge-reorganization allostery in enzyme-antibody binding.

Contribution

It demonstrates that charged substrates can modulate charge-reorganization allostery in proteins, expanding understanding of allosteric regulation beyond conformational changes.

Findings

Charge redistribution can lead to allosteric effects in proteins.

Nucleotide substrates modulate charge-reorganization allostery significantly.

ATP binding reduces CRA by more than 50%.

Abstract

Protein function may be modulated by an event occurring far away from the functional site, a phenomenon termed allostery. While classically allostery involves conformational changes, we recently observed that charge redistribution within an antibody can also lead to an allosteric effect, modulating the kinetics of binding to target antigen. In the present study, we study the association of a poly-histidine tagged enzyme (phosphoglycerate kinase, PGK) to surface-immobilized anti-His antibodies, finding a significant Charge-Reorganization Allostery (CRA) effect. We further observe that the negatively charged nucleotide substrates of PGK modulate CRA substantially, even though they bind far away from the His-tag-antibody interaction interface. In particular, binding of ATP reduces CRA by more than 50%. The results indicate that CRA may be affected by charged substrates bound to a protein and provide further insight into the role of charge redistribution in protein function.