Folding and self-assembly of a small protein complex

Area of Science:

• Protein biophysics
• Computational biology
• Molecular dynamics

Background:

• The synthetic homotetrameric ββα (BBAT1) protein is a small, 84-residue model system ideal for studying protein self-assembly and interactions.
• Its stable quaternary structure and ββα fold make it a valuable subject for biophysical investigation.

Purpose of the Study:

• To elucidate the folding and association pathway of the BBAT1 protein.
• To investigate the structural ensemble of the tetramer at room temperature.
• To understand the environmental factors influencing the energetically favored crystal structure.

Main Methods:

• Replica exchange molecular dynamics simulations were employed.
• The coarse-grain UNRES force field was utilized for simulations.

Main Results:

• The folding and association pathway involves three distinct steps.
• Tetramer association precedes and facilitates the folding of individual protein chains.
• At room temperature, the tetramer exists as a diverse structural ensemble.
• The crystal structure is favored only in dense, crystal-like environments.

Conclusions:

• Protein folding can be promoted by association, a mechanism potentially applicable to intrinsically disordered proteins.
• The study provides a detailed model for understanding protein self-assembly and folding dynamics.