Condensates Formed by Prion-like Low-complexity Domains Have Small-world Network Structures and Interfaces Defined by Expanded Conformations

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Dec 13

PMID 36513655

Authors

Mina Farag

Samuel R Cohen

Wade M Borcherds

Anne Bremer

Tanja Mittag

Rohit V Pappu

Affiliations

Soon will be listed here.

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.

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