Strategies for Conditional Regulation of Proteins

Abstract

Design of the next-generation of therapeutics, biosensors, and molecular tools for basic research requires that we bring protein activity under control. Each protein has unique properties, and therefore, it is critical to tailor the current techniques to develop new regulatory methods and regulate new proteins of interest (POIs). This perspective gives an overview of the widely used stimuli and synthetic and natural methods for conditional regulation of proteins.

Spatiotemporal Organization of Functional Cargoes by Light-Switchable Condensation in Escherichia coli Cells

“…Light-controlled optogenetic tools are intriguing for dynamic regulation , due to their precise control over protein–protein interactions in a spatiotemporal and reversible manner. As optogenetic molecules are relatively large in molecular weights and prone to aggregation upon overexpression in prokaryotic cells, fusion expression of optogenetic molecules with scaffolding and client proteins often leads to the formation of insoluble and inactive aggregates, ,,, which adversely affects the functioning of the resulting condensates and the realization of reversible and repeatable regulation. To address this challenge, here, we propose a modular framework for the organization of synthetic condensates by decoupling condensate formation and client recruitment/release (Scheme ).…”

Nanobody-targeted conditional antimicrobial therapeutics

“…7 Activatable or conditional therapeutics are a promising therapeutic modality to enhance the efficacy or the safety profile of small-molecule drugs and biologics. [8][9][10][11] Specific triggers (e.g. pH, hypoxia, redox, reactive oxygen species, and enzymes) at the diseased sites are exploited to release or convert pro-therapeutics into their active forms.…”