Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties

Abstract

These folds are determined by both protein sequence and solvent properties, and determine protein function. [2] Therefore, the diversity of protein folds in cells allows them to carry out a range of functions, such as catalysis of different reactions. Functional versatility within polypeptide chains is further increased through the presence of multiple independently folding sequences, defined as domains, each associated with distinct functions, such as dimerization or responsiveness to a regulator. However, it is now recognized that some proteins do not have defined conformations, or feature domains that are intrinsically disordered (intrinsically disordered regions, IDRs), and that these confer function by mediating context-dependent proteinprotein interactions. [3] The concept of self-organization of proteins is also applied to assemblies of multiple proteins, in which case it refers to formation of dynamic multi-component structures, [4] including certain oligomeric complexes, filaments, and phase-separated assemblies. In phase-separated assemblies, of which a range exist, IDR-containing proteins form a dense phase within the cytoplasm, commonly referred to as biomolecular condensates. [5] As for folds, the formation of these assemblies depends both on interactions between the phase-separating proteins, which can be mediated by their IDRs, and between these proteins and the surrounding solution. Within the cytoplasm, these phase-separated "droplets" commonly contain RNA, in which case they are referred to as ribonucleoprotein (RNP) granules. They can be considered to have "emergent properties:" certain characteristics can be ascribed to assemblies that are not properties of individual constituent proteins. [6] For instance, biomolecular condensates can display liquid-like properties such as fusion and wetting, which led to their identification as phase-separated droplets. [7] These properties allow them to function as dynamic membraneless organelles, or compartments. This compartmentalization is commonly referred to as occurring on the "mesoscale," which is defined as that range of lengths larger than the size of individual molecular machinery such as ribosomes, but smaller than that of the whole cell. [8] The sensitivity of protein folds and macromolecular interactions to local environmental conditions confers both regulatory potential and risk of loss of function in "extreme" conditions. This regulatory potential is exemplified by and has beenThe cytoplasm is an aqueous, highly crowded solution of active macromolecules. Its properties influence the behavior of proteins, including their folding, motion, and interactions. In particular, proteins in the cytoplasm can interact to form phase-separated assemblies, so-called biomolecular condensates. The interplay between cytoplasmic properties and protein condensation is critical in a number of functional contexts and is the subject of this review. The authors first describe how cytoplasmic properties can affect protein behavior, in particular condensate formation...

Stress‐dependent macromolecular crowding in the mitochondrial matrix

“…A key phenomenon associated with macromolecular crowding is that it reduces the translational mobility of solutes with a similar or larger size than the crowder to a greater extent than the mobility of smaller solutes (e.g., Mika et al , 2010 ; Delarue et al , 2018 ; Junker et al , 2019 ; Van Tartwijk & Kaminski, 2022 ). The solvent‐dependent translational mobility of a solute in the mitochondrial matrix is quantitatively described by its solvent‐dependent diffusion constant (D solvent ).…”

“…This will affect their chemical reaction rates and/or molecular target finding (Dey & Bhattacherjee, 2019 ; Weilandt & Hatzimanikatis, 2019 ). Macromolecular crowding can also induce “molecular sieving” effects, which alter the translational mobility of biomolecules in an MW/size‐dependent manner (Papadopoulos et al , 2000 ; Mika et al , 2010 ; Junker et al , 2019 ; Van Tartwijk & Kaminski, 2022 ). In this sense, macromolecular crowding will reduce the diffusion coefficient of larger tracer molecules to a greater extent than predicted by the Stokes–Einstein equation (Mika et al , 2010 ; Delarue et al , 2018 ; Junker et al , 2019 ).…”

Protein aggregation is a consequence of the dormancy-inducing membrane toxin TisB inEscherichia coli

“…The primary action of TisB is breakdown of the proton motive force, which is similar to the action of protonophores and likely leads to disturbance of pH homeostasis and acidification of the cytoplasm (83,84). Potentially, the drop in intracellular pH initiates the aggregation process (85), but this needs further investigation. Interestingly, pH-driven protein aggregation and acidification have been associated with dormancy and increased stress tolerance in both yeast and bacteria (86,87), and may also contribute to TisB-induced dormancy and persistence.…”

Toward Artificial Cell‐Mediated Tissue Engineering: A New Perspective

“…Especially, their superior permeability makes them stand out for advanced cell biology and related tissue engineering applications. [50][51][52][53][54][55] Still, most of the particle-based tissue engineering approaches suffer from limited temporal control and they are rarely interactive with cells in their environment despite advanced delivery mechanisms. [56] Therefore, more intelligent systems that can better mimic extra and intracellular functions are required to develop more advanced tissue engineering approaches.…”