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Multimolecular Competition Effect as a Modulator of Protein Localization and Biochemical Networks in Cell-Size Space

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Kohyama,  Shunshi
Schwille, Petra / Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry, Max Planck Society;

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引用

Nishikawa, S., Sato, G., Takada, S., Kohyama, S., Honda, G., Yanagisawa, M., Hori, Y., Doi, N., Yoshinaga, N., & Fujiwara, K. (2023). Multimolecular Competition Effect as a Modulator of Protein Localization and Biochemical Networks in Cell-Size Space. Advanced Science,. doi:10.1002/advs.202308030.


引用: https://hdl.handle.net/21.11116/0000-000E-1DA5-8
要旨
Cells are small, closed spaces filled with various types of macromolecules. Although it is shown that the characteristics of biochemical reactions in vitro are quite different from those in living cells, the role of the co-existence of various macromolecules in cell-size space remains still elusive. Here, using a constructive approach, it is demonstrated that the co-existence of various macromolecules themselves has the ability to tune protein localization for spatiotemporal regulation and a biochemical reaction system in a cell-size space. Both experimental and theoretical analyses reveal that enhancement of interfacial effects by a large surface-area-to-volume ratio facilitates membrane localization of molecules in the cell-size space, and the interfacial effects are alleviated by competitive binding to lipid membranes among multiple proteins even if their membrane affinities are weak. These results indicate that competition for membrane binding among various macromolecules in the cell-size space plays a role in regulating the spatiotemporal molecular organization and biochemical reaction networks. These findings shed light on the importance of surrounding molecules for biochemical reactions using purified elements in small spaces.
In confined cell-size spaces, membrane localization of proteins is enhanced due to the cell-size space effect. This enhanced membrane localization disturbs biochemical networks such as spatiotemporal regulation and protein expression. It is found that the competitive binding of surrounding macromolecules to membranes cancels this effect, ensuring the functionality of biochemical systems.image