Multivalent weak contacts shape chaperone-nascent protein interactions

Area of Science:

• Molecular biology
• Biophysics
• Protein folding

Background:

• Molecular chaperones are essential for preventing protein misfolding within cells.
• Trigger factor is a ribosome-associated chaperone that assists nascent polypeptide folding.
• The precise mechanisms of trigger factor's dynamic interactions with emerging proteins are not fully understood.

Purpose of the Study:

• To directly observe and characterize the interactions between trigger factor and ribosome-bound nascent proteins.
• To elucidate the nature and dynamics of trigger factor binding as polypeptide chains elongate.

Main Methods:

• Single-molecule fluorescence techniques.
• Optical tweezers to apply mechanical force.
• Direct observation of trigger factor binding to client proteins at various chain lengths.

Main Results:

• Trigger factor binding is characterized by multiple weak, dynamic interactions.
• These interactions are established after ribosome docking and evolve during polypeptide elongation.
• Mechanical force disrupts trigger factor binding, supporting a multivalent interaction model.

Conclusions:

• Trigger factor employs a multivalent binding strategy to interact with nascent proteins.
• This dynamic binding mode likely stabilizes proteins against misfolding while allowing conformational exploration.
• Understanding these interactions provides insights into cotranslational protein folding.