Disordered regions of human eIF4B orchestrate a dynamic self-association landscape.

Area of Science:

• Molecular Biology
• Biophysics
• Cell Biology

Background:

• Eukaryotic translation initiation factor 4B (eIF4B) is crucial for cap-dependent translation and is overexpressed in cancer.
• Its intrinsically disordered region (IDR) is largely uncharacterized due to challenges in structural determination.
• eIF4B's role in stress granule formation is also under investigation.

Purpose of the Study:

• To elucidate the molecular mechanisms and dynamics of the intrinsically disordered region (IDR) of eIF4B.
• To understand how eIF4B transitions from monomers to a condensed phase and forms dynamic oligomers.
• To investigate the factors influencing eIF4B self-association and its potential regulation.

Main Methods:

• Integration of single-molecule spectroscopy and molecular simulations.
• Characterization of conformational ensembles and intra/intermolecular dynamics.
• Assessment of eIF4B behavior under varying ionic strength and molecular crowding conditions.

Main Results:

• Demonstrated that the eIF4B IDR orchestrates a transition from monomers to a condensed phase involving dynamic oligomer formation.
• Characterized the conformational ensembles and dynamics during oligomerization using advanced spectroscopy and simulations.
• Revealed sensitivity of eIF4B self-association to ionic strength and molecular crowding.

Conclusions:

• The eIF4B IDR plays a key role in regulating protein self-association and phase transitions.
• These findings provide insights into the dynamic behavior of intrinsically disordered proteins in cellular environments.
• The study suggests potential regulatory mechanisms for eIF4B function through post-translational modifications or environmental changes.