Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: The physics of liquid-to-solid transitions in multi-domain protein condensates Many RNA-binding proteins (RBPs) that assemble into membraneless organelles, have a common architecture including disordered prion-like domain (PLD) and folded RNA-binding domain (RBD). An enrichment of PLD within the condensed phase gives rise to formation, on longer time scales, amyloid-like fibrils (aging). In this study, we employ coarse-grained Langevin dynamics simulations to explore the physical basis for the structural diversity in condensed phases of multi-domain RBPs. We discovered a highly cooperative first order transition between disordered structures and an ordered phase whereby chains of PLD organize in fibrils with high nematic orientational order. An interplay between homo-domain (PLD-PLD) and hetero-domain (PLD-RBD) interactions results in variety of structures with distinct spatial architectures. Interestingly, the different structural phases also exhibit vastly different intra-cluster dynamics of proteins, with diffusion coefficients 5 (disordered structures) to 50 times (ordered structures) lower than that of the dilute phase. Cooperativity of this liquid-solid transition makes fibril formation highly malleable to mutations or post-translational modifications. Our results provide a mechanistic understanding of how multi-domain RBPs could form assemblies with distinct structural and material properties.

Significance StatementAssembly of proteins and nucleic acids into dense, liquid-like pockets is associated with several key functions including stress response, gene-regulation, DNA-repair and RNA processing. Several RNA binding proteins such as FUS are known to form liquid-like condensates that progressively harden into more dynamically, solid-like structures, a phenomenon that gets accelerated by disease mutations. In this study, we discover the mechanistic origins of this transition and show that small mutational or posttranslational modifications could result in sharp disorder-order transitions that could characterize accelerated liquid-solid transition in disease mutants.
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The categories of this paper are: epidemiology
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The categories of this paper are: molecular
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The categories of this paper are: biology
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The categories of this paper are: pharmacology
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The categories of this paper are: immunology
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The categories of this paper are: evolutionary
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The categories of this paper are: plant
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The categories of this paper are: microbiology
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The categories of this paper are: paleontology
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The categories of this paper are: scientific
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The categories of this paper are: developmental
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The categories of this paper are: and
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The categories of this paper are: ecology
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The categories of this paper are: cognition
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The categories of this paper are: bioengineering
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The categories of this paper are: pathology