Abstract
Interaction between membrane proteins and ligands plays a key role in governing a wide spectrum of cellular processes. These interactions can provide a cooperative-type regulation of protein function. A wide variety of proteins, including enzymes, channels, transporters, and receptors, displays cooperative behavior in their interactions with ligands. Moreover, the ligands involved encompass a vast diversity and include specific molecules or ions that bind to specific binding sites. In this review, our particular focus is on the interaction between integral membrane proteins and ligands that can present multiple “binding sites”, such as protons or membrane phospholipids. The study of the interaction that protons or lipids have with membrane proteins often presents challenges for classical mechanistic modeling approaches. In this regard, we show that, like Hill’s pioneering work on hemoglobin regulation, phenomenological modeling constitutes a powerful tool for capturing essential features of these systems.
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This work was supported by ANPCYT (PICT 2019- 02768 to FLGF and PICT 2017–0244 and PICT 2019–00387 to KA) and UBA (UBACYT 2018 0178 to KA and 0306 to FLGF).
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FLGF and KA contributed to the study conception and design. Material preparation, data collection, and analysis were performed by GZDP, AR, and VV. The first draft of the manuscript was written by KA and FLGF and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Zerbetto De Palma, G., Recoulat Angelini, A.A., Vitali, V. et al. Cooperativity in regulation of membrane protein function: phenomenological analysis of the effects of pH and phospholipids. Biophys Rev 15, 721–731 (2023). https://doi.org/10.1007/s12551-023-01095-0
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DOI: https://doi.org/10.1007/s12551-023-01095-0