Interaction-Dependent Secondary Structure of Peptides in Biomolecular Condensates.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : American Chemical Society
      Original Publication: Easton, Pa. [etc.]
    • Subject Terms:
      Biomolecular Condensates*/chemistry ; Peptides*/chemistry ; Molecular Dynamics Simulation*; Hydrogen Bonding ; Protein Structure, Secondary ; RNA/chemistry ; Polyethylene Glycols/chemistry
    • Abstract:
      Biomolecular condensates provide a mechanism for compartmentalization of biomolecules in eukaryotic cells. These liquid-like condensates are formed via liquid-liquid phase separation, by a plethora of interactions, and can mediate several biological processes in healthy cells. Expansions of dipeptide repeat proteins, DPRs, in which arginine rich DPRs like poly-proline-arginine (PR), and poly-glycine-arginine (GR), partition RNA into condensates can however induce cell toxicity. Here, we use (GR) 20 as a model for biological poly-GR and condense it using either excluded volume interactions with polyethylene glycol (PEG) as a crowder or direct electrostatic interactions with RNA oligomers. Using two-dimensional infrared (2D IR) spectroscopy, we observe that (GR) 20 condensed through an excluded volume forms β-sheet structures, whereas (GR) 20 condensed with RNA forms loops. We also investigate local hydrogen-bond dynamics in the condensate and compare the measurements with molecular dynamics simulations. Hydrogen bond lifetimes undergo a marked slowdown compared to dynamics in the dilute phase. This is representative of confined water within the percolated networks inside the condensate due to the interaction present in the condensate disrupting H-bond networks. Overall, our results show that both protein structure and dynamics are inherently dependent on the type of interactions that stabilize the condensates.
    • Accession Number:
      0 (Peptides)
      63231-63-0 (RNA)
      3WJQ0SDW1A (Polyethylene Glycols)
    • Publication Date:
      Date Created: 20241126 Date Completed: 20241211 Latest Revision: 20241211
    • Publication Date:
      20241211
    • Accession Number:
      10.1021/jacs.4c11226
    • Accession Number:
      39591652