Beta turn propensity and a model polymer scaling exponent identify intrinsically disordered phase-separating proteins
| Autor: | Nicholas C. Fitzkee, Elisia A. Paiz, John J. Correia, Jeffre H. Allen, Loren E. Hough, Steven T. Whitten |
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| Rok vydání: | 2021 |
| Předmět: |
ASA
accessible surface area Polymers Nucleation IDP intrinsically disordered protein Biochemistry Protein–protein interaction Accessible surface area protein sequence Protein sequencing Phase (matter) Databases Protein Molecular Biology Scaling CHASA conditional hydrophobic accessible surface area SCD sequence charge decoration Small-angle X-ray scattering Chemistry SAXS small-angle X-ray scattering SHD sequence hydropathy decoration ID intrinsically disordered Cell Biology intrinsically disordered protein protein self-assembly SCOPe structural classification of proteins extended Intrinsically Disordered Proteins LLPS liquid–liquid phase separation IDR intrinsically disordered region PS phase separating protein–protein interaction subcellular organelle Chemical physics ELP elastin-like polypeptide Exponent Protein Conformation beta-Strand Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Popis: | The complex cellular milieu can spontaneously demix, or phase separate, in a process controlled in part by intrinsically disordered (ID) proteins. A protein's propensity to phase separate is thought to be driven by a preference for protein–protein over protein–solvent interactions. The hydrodynamic size of monomeric proteins, as quantified by the polymer scaling exponent (v), is driven by a similar balance. We hypothesized that mean v, as predicted by protein sequence, would be smaller for proteins with a strong propensity to phase separate. To test this hypothesis, we analyzed protein databases containing subsets of proteins that are folded, disordered, or disordered and known to spontaneously phase separate. We find that the phase-separating disordered proteins, on average, had lower calculated values of v compared with their non-phase-separating counterparts. Moreover, these proteins had a higher sequence-predicted propensity for β-turns. Using a simple, surface area-based model, we propose a physical mechanism for this difference: transient β-turn structures reduce the desolvation penalty of forming a protein-rich phase and increase exposure of atoms involved in π/sp2 valence electron interactions. By this mechanism, β-turns could act as energetically favored nucleation points, which may explain the increased propensity for turns in ID regions (IDRs) utilized biologically for phase separation. Phase-separating IDRs, non-phase-separating IDRs, and folded regions could be distinguished by combining v and β-turn propensity. Finally, we propose a new algorithm, ParSe ( par tition se quence), for predicting phase-separating protein regions, and which is able to accurately identify folded, disordered, and phase-separating protein regions based on the primary sequence. |
| Databáze: | OpenAIRE |
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