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

Autor: Davis RB; Department of Physics, University at Buffalo, Buffalo, NY, 14260, USA., Supakar A; Department of Biological Sciences, University at Buffalo, Buffalo, NY, 14260, USA., Ranganath AK; Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, 14260, USA., Moosa MM; Department of Physics, University at Buffalo, Buffalo, NY, 14260, USA., Banerjee PR; Department of Physics, University at Buffalo, Buffalo, NY, 14260, USA. prbanerj@buffalo.edu.; Department of Biological Sciences, University at Buffalo, Buffalo, NY, 14260, USA. prbanerj@buffalo.edu.; Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, NY, 14260, USA. prbanerj@buffalo.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 07; Vol. 15 (1), pp. 1168. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1038/s41467-024-44945-5
Abstrakt: 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 (mSWI/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 condensates. Heterotypic PLD-mediated positive cooperativity in protein-protein interaction networks is likely to play key roles in the co-phase separation of mSWI/SNF complex with transcription factors containing homologous low-complexity domains.
(© 2024. The Author(s).)
Databáze: MEDLINE
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