Nonspecific interactions can lead to liquid-liquid phase separation in coiled-coil proteins models

Area of Science:

• Biophysics
• Molecular Biology
• Cell Biology

Background:

• Liquid-liquid phase separation (LLPS) is a key cellular mechanism for organizing biomolecules.
• Coiled-coil (CC) proteins, like pericentrin and spd-5, are implicated in LLPS, potentially via their multiple CC domains.

Purpose of the Study:

• To investigate the role of specific versus nonspecific interactions mediated by CC domains in LLPS.
• To explore how linker segments and intra-chain contacts affect LLPS propensity in CC proteins.

Main Methods:

• Computational studies using designed proteins with varying CC interaction specificities.
• Analysis of the impact of linker structure/dynamics and intra-chain CC contacts on LLPS.

Main Results:

• CC proteins with specific interactions exhibit higher LLPS propensity than those with nonspecific interactions.
• Modifying linker segments and increasing intra-chain CC contacts can enhance LLPS for nonspecifically interacting CC proteins.
• Linker segments play a significant role in protein LLPS, beyond the interaction domains themselves.

Conclusions:

• CC domain interactions, particularly specific ones, are crucial for driving LLPS.
• Non-specific interactions can also drive LLPS, with propensity tunable via linker properties and intra-chain contacts.
• This work highlights the importance of protein features beyond traditional 'stickers' in biomolecular condensate formation.