期刊论文详细信息
Biomolecules
Molecular Crowding Tunes Material States of Ribonucleoprotein Condensates
MahdiMuhammad Moosa1  Wei Wang2  Taranpreet Kaur2  Ibraheem Alshareedah2  PriyaR. Banerjee2  Jason Ngo2 
[1] Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA;Department of Physics, University at Buffalo, SUNY, NY 14260, USA;
关键词: membraneless organelles;    optical tweezer;    liquid–liquid phase separation;    protein diffusion;    depletion interaction;    entropic force;    low-complexity sequences;    intrinsically disordered proteins;   
DOI  :  10.3390/biom9020071
来源: DOAJ
【 摘 要 】

Ribonucleoprotein (RNP) granules are membraneless liquid condensates that dynamically form, dissolve, and mature into a gel-like state in response to a changing cellular environment. RNP condensation is largely governed by promiscuous attractive inter-chain interactions mediated by low-complexity domains (LCDs). Using an archetypal disordered RNP, fused in sarcoma (FUS), here we study how molecular crowding impacts the RNP liquid condensation. We observe that the liquid⁻liquid coexistence boundary of FUS is lowered by polymer crowders, consistent with an excluded volume model. With increasing bulk crowder concentration, the RNP partition increases and the diffusion rate decreases in the condensed phase. Furthermore, we show that RNP condensates undergo substantial hardening wherein protein-dense droplets transition from viscous fluid to viscoelastic gel-like states in a crowder concentration-dependent manner. Utilizing two distinct LCDs that broadly represent commonly occurring sequence motifs driving RNP phase transitions, we reveal that the impact of crowding is largely independent of LCD charge and sequence patterns. These results are consistent with a thermodynamic model of crowder-mediated depletion interaction, which suggests that inter-RNP attraction is enhanced by molecular crowding. The depletion force is likely to play a key role in tuning the physical properties of RNP condensates within the crowded cellular space.

【 授权许可】

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