期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：35
DOI：10.1073/pnas.2204735119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The role of well-placed charges within proteins in mediating biological functions, from protein-protein association to enzyme kinetics, is well documented. Here, we go beyond this static picture and show that charge motions can exert significant effects on protein function. Injecting charge from a photosensitizer, we demonstrate a threefold decrease in enzymatic activity and a twofold increase of antibody-antigen binding. These effects depend on the specific position of the photosensitizer on the protein. Our results point to charge reorganization as a form of allostery that complements known allosteric mechanisms such as conformational changes and dynamics.
Considerable electric fields are present within living cells, and the role of bioelectricity has been well established at the organismal level. Yet much remains to be learned about electric-field effects on protein function. Here, we use phototriggered charge injection from a site-specifically attached ruthenium photosensitizer to directly demonstrate the effect of dynamic charge redistribution within a protein. We find that binding of an antibody to phosphoglycerate kinase (PGK) is increased twofold under illumination. Remarkably, illumination is found to suppress the enzymatic activity of PGK by a factor as large as three. These responses are sensitive to the photosensitizer position on the protein. Surprisingly, left (but not right) circularly polarized light elicits these responses, indicating that the electrons involved in the observed dynamics are spin polarized, due to spin filtration by protein chiral structures. Our results directly establish the contribution of electrical polarization as an allosteric signal within proteins. Future experiments with phototriggered charge injection will allow delineation of charge rearrangement pathways within proteins and will further depict their effects on protein function.
