Lessons from equilibrium statistical physics regarding the assembly of protein complexes

Area of Science:

• Biophysics
• Systems Biology
• Evolutionary Biology

Background:

• Cellular functions rely on protein complexes due to physical limitations on individual protein size.
• Protein complex assembly is challenged by cellular noise and the laws of physics.
• Reliable assembly is crucial for cellular function and survival.

Purpose of the Study:

• To establish a theoretical framework for reliable protein complex assembly.
• To investigate the physical and thermodynamic principles governing protein complex formation.
• To identify conditions promoting error-free assembly of multiple protein complexes.

Main Methods:

• Development of an equilibrium thermodynamic model for self-assembly.
• Analysis of four distinct assembly behaviors: diluted solution, liquid mixture, chimeric, and multifarious assembly.
• Examination of component heterogeneity and sparsity as key parameters.

Main Results:

• Identified a 'multifarious assembly' regime where diverse complexes coexist without erroneous chimeric structures.
• Demonstrated that heterogeneous complex composition and sparse component usage are critical for this regime.
• Observed that biological protein systems appear to have evolved to meet these conditions.

Conclusions:

• Cellular evolution has likely optimized protein complex systems for reliable and diverse assembly.
• Heterogeneity and sparsity are key evolutionary strategies for robust protein complex formation.
• The study provides a foundation for understanding the physics of biological self-assembly.