The Trigger Factor Chaperone Encapsulates and Stabilizes Partial Folds of Substrate Proteins

Area of Science:

• Molecular Biology
• Biophysics
• Protein Folding

Background:

• Understanding chaperone-substrate interactions is crucial for protein folding.
• Transient nature of complexes and large system sizes challenge atomistic insight.
• Trigger Factor (TF) is known to bind unfolded proteins and assist folding.

Purpose of the Study:

• To provide atomistic insights into how Trigger Factor (TF) facilitates protein folding.
• To elucidate the mechanisms of TF's interaction with unfolded and partially folded protein chains.

Main Methods:

• All-atom molecular dynamics (MD) simulations were employed.
• Investigated TF's interactions with both unfolded and partially folded protein structures.

Main Results:

• TF's appendage tips are crucial for initial interactions with unfolded and partially folded chains.
• TF kinetically traps unfolded chains, preventing non-native end-to-end contacts.
• TF mechanically stabilizes partially folded structures via a unique encapsulation mechanism, distinct from GroEL.

Conclusions:

• TF's encapsulation mechanism protects diverse protein structures from misfolding and aggregation.
• The study suggests ATP is not required for TF-mediated encapsulation and liberation.
• TF's flexible structure and appendage tips play key roles in its chaperone function.