A cradle for new proteins: trigger factor at the ribosome

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Newly synthesized proteins emerge from the ribosome unfolded and are susceptible to aggregation and degradation.
• Ribosome-associated chaperones play a crucial role in preventing misfolding during protein synthesis.
• Trigger factor is the primary chaperone interacting with nascent chains in bacteria.

Purpose of the Study:

• To elucidate the structural basis of trigger factor's interaction with the ribosome and nascent proteins.
• To understand the mechanism by which trigger factor facilitates co-translational protein folding.
• To integrate structural and biochemical data for a comprehensive view of trigger factor's function.

Main Methods:

• X-ray crystallography was used to determine the structures of trigger factor and its complex with the large ribosomal subunit.
• Biochemical assays were employed to study the interplay of trigger factor with other chaperones and nascent chain-binding factors.

Main Results:

• Crystal structures revealed trigger factor's 'dragon-shaped' fold and a hydrophobic cradle arching over the ribosomal tunnel exit.
• This structure allows trigger factor to effectively shield newly synthesized proteins as they emerge.
• Biochemical data confirmed trigger factor's role in preventing aggregation and facilitating folding during translation.

Conclusions:

• Trigger factor's unique structure enables it to bind the ribosome and protect nascent polypeptides.
• The chaperone's 'dragon-shaped' fold is critical for its function in co-translational protein folding.
• These findings provide a detailed mechanistic understanding of trigger factor's essential role in bacterial protein homeostasis.