Conformational Entropy of Intrinsically Disordered Proteins Bars Intruders from Biomolecular Condensates.

Area of Science:

• Biochemistry
• Cell Biology
• Biophysics

Background:

• Eukaryotic cells contain numerous biomolecular condensates.
• These condensates are rich in proteins and RNA with intrinsically disordered regions (IDRs).
• IDRs are known to play various roles in condensate formation and function.

Purpose of the Study:

• To investigate the role of intrinsically disordered regions (IDRs) in excluding molecules from biomolecular condensates.
• To propose and analyze the entropic barrier created by IDRs.

Main Methods:

• Utilized polymer theory and sticker-spacer simulations.
• Developed a size-exclusion theory for biomolecular condensates.

Main Results:

• IDRs create an entropic barrier, excluding 'intruders' based on their size and concentration.
• Insertion free energy scales with IDR concentration and intruder size.
• Particles as small as 4 nm can be 97% excluded at realistic IDR concentrations.
• Favorable interactions are required for molecules to overcome this barrier and be recruited.

Conclusions:

• IDRs play a critical role in excluding unwanted molecules from condensates via an entropic mechanism.
• This size-exclusion principle may be a generic feature of biological condensates across different organisms.
• Understanding this mechanism is key to comprehending condensate regulation and function.