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Heterotypic interactions in the dilute phase can drive co-condensation of prion-like low-complexity domains of FET proteins and mammalian SWI/SNF complex.

Richoo B DavisAishwarya Kanchi RanganathMahdi Muhammad MoosaPriya R Banerjee
Published in: bioRxiv : the preprint server for biology (2023)
Prion-like domains (PLDs) are low-complexity protein sequences enriched within nucleic acid-binding proteins including those involved in transcription and RNA processing. PLDs of FUS and EWSR1 play key roles in recruiting chromatin remodeler mammalian SWI/SNF complex to oncogenic FET fusion protein condensates. Here, we show that disordered low-complexity domains of multiple SWI/SNF subunits are prion-like with a strong propensity to undergo intracellular phase separation. These PLDs engage in sequence-specific heterotypic interactions with the PLD of FUS in the dilute phase at sub-saturation conditions, leading to the formation of PLD co-condensates. In the dense phase, homotypic and heterotypic PLD interactions are highly cooperative, resulting in the co-mixing of individual PLD phases and forming spatially homogeneous ternary co-condensates. Heterotypic PLD-mediated positive cooperativity in protein-protein interaction networks is likely to play key roles in the assembly of SWI/SNF complexes and their co-phase separation with transcription factors containing homologous low-complexity domains.
Keyphrases
  • transcription factor
  • protein protein
  • nucleic acid
  • dna damage
  • dna repair
  • gold nanoparticles
  • genome wide identification