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Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations

Author

Listed:
  • Mina Farag

    (Washington University in St. Louis)

  • Samuel R. Cohen

    (Washington University in St. Louis)

  • Wade M. Borcherds

    (St. Jude Children’s Research Hospital)

  • Anne Bremer

    (St. Jude Children’s Research Hospital)

  • Tanja Mittag

    (St. Jude Children’s Research Hospital)

  • Rohit V. Pappu

    (Washington University in St. Louis)

Abstract

Biomolecular condensates form via coupled associative and segregative phase transitions of multivalent associative macromolecules. Phase separation coupled to percolation is one example of such transitions. Here, we characterize molecular and mesoscale structural descriptions of condensates formed by intrinsically disordered prion-like low complexity domains (PLCDs). These systems conform to sticker-and-spacers architectures. Stickers are cohesive motifs that drive associative interactions through reversible crosslinking and spacers affect the cooperativity of crosslinking and overall macromolecular solubility. Our computations reproduce experimentally measured sequence-specific phase behaviors of PLCDs. Within simulated condensates, networks of reversible inter-sticker crosslinks organize PLCDs into small-world topologies. The overall dimensions of PLCDs vary with spatial location, being most expanded at and preferring to be oriented perpendicular to the interface. Our results demonstrate that even simple condensates with one type of macromolecule feature inhomogeneous spatial organizations of molecules and interfacial features that likely prime them for biochemical activity.

Suggested Citation

  • Mina Farag & Samuel R. Cohen & Wade M. Borcherds & Anne Bremer & Tanja Mittag & Rohit V. Pappu, 2022. "Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35370-7
    DOI: 10.1038/s41467-022-35370-7
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    1. Pilong Li & Sudeep Banjade & Hui-Chun Cheng & Soyeon Kim & Baoyu Chen & Liang Guo & Marc Llaguno & Javoris V. Hollingsworth & David S. King & Salman F. Banani & Paul S. Russo & Qiu-Xing Jiang & B. Tra, 2012. "Phase transitions in the assembly of multivalent signalling proteins," Nature, Nature, vol. 483(7389), pages 336-340, March.
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    3. Ibraheem Alshareedah & Mahdi Muhammad Moosa & Matthew Pham & Davit A. Potoyan & Priya R. Banerjee, 2021. "Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Jiang, R. & Murthy, D.N.P., 2011. "A study of Weibull shape parameter: Properties and significance," Reliability Engineering and System Safety, Elsevier, vol. 96(12), pages 1619-1626.
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