Given the success of Volume I
of this Research Topic, and how rapid the subject area is evolving, we are pleased to announce the launch of Molecular Determinants of Protein Assemblies in Health and Disease - Volume II
Proteins can self-assemble to form supramolecular entities called “aggregates”. Protein aggregation is a phenomenon that can be both directed and inadvertent; the latter is often proceeded by proteotoxic insults wherein proteins self-associate to form higher-order structures implicated in disease. Conversely, certain proteins have evolved to self-assemble to perform beneficial roles in the organism. Accumulating evidence highlights protein self-assembles not only into amorphous or amyloid-like aggregates but also into biomolecular condensates with liquid-like or gel-like material properties in physiological settings via a mechanism called phase-separation. In these condensates, crosstalk between proteins and nucleic acids has often been observed and they are linked to diverse processes including stress response, DNA repair, and gene regulation.
Proteins can switch between soluble and condensed/aggregated states in response to subtle changes in intrinsic (post-translational modifications, mutations) and extrinsic factors (pH, temperature, salt concentration), and dependent on the crowding of their environment. Once phase-separated, proteins can often also progressively transition to more aggregated states, even the amyloid-like state. Thus, while the functional form of protein assemblies could span several material phases, aberrant transitions between these phases could result in loss of function or toxic gain of function, a phenomenon expedited by mutations and other factors like alternative splicing.
Given that protein function typically hinges on the ability to interact with other proteins or form higher-order structures, the cellular proteostasis mechanisms must ensure tight regulation of their synthesis, folding, self-assembly, disassembly and degradation. Identifying the molecular driving forces for the formation and turnover of biomolecular condensates/aggregates is essential to understand how living systems deal with the delicate balance between function and disease and how this equilibrium is impacted by aging. Moreover, studying the active and passive mechanisms that dictate the fate of protein or protein-nucleic acids assemblies becomes crucial to not only understanding how these assemblies function but also from the perspective of cellular evolution.
Having successfully completed Volume 1.0 of this Research Topic encompassing various aspects of protein structure, function, aggregation, and biomolecular condensate formation, we are now heading towards launching Volume 2.0 showcasing more exciting themes. The new volume aims to expound on the structural and regulatory determinants of protein assemblies, in particular, of the biomolecular condensates implicated in functional or pathological roles. We invite Original Research, Review, Mini-Review, Perspective, Hypothesis and Theory, Case reports, and Opinion articles including, but not limited to the following themes:
● New physiological functions of biomolecular condensates
● Biomolecular condensates in diseases
● Factors influencing the formation and dissociation of “functional protein assemblies” such as protein condensates and functional amyloids
● Biomolecular self-assembly and cellular evolution
● Deregulation of protein assembly during aging
● Cellular degradation of misfolded proteins, aggregates, and condensates
● Post-translational modifications and their role in regulating biomolecular phase separation
● Cytoplasmic macromolecular crowding as a cause (or consequence) of biomolecular condensation/ aggregate formation
● New model organisms/systems to study protein aggregation
● Design of functional synthetic protein assemblies
● Structural diversity of protein aggregatesProf. Salvador Ventura Zamora holds patents related to this Research Topic, all other Topic Editors declare no conflict of interest