Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Nascent polypeptide chains emerging from ribosomes require assistance for proper folding.
• Ribosome-associated chaperones play a crucial role in co-translational protein folding.
• Trigger factor is a well-characterized chaperone involved in this process.

Purpose of the Study:

• To determine the high-resolution crystal structure of Escherichia coli trigger factor.
• To elucidate the structure of trigger factor's ribosome-binding domain in complex with a large ribosomal subunit.
• To understand the mechanism by which trigger factor facilitates co-translational protein folding.

Main Methods:

• X-ray crystallography was used to obtain a 2.7 Å resolution structure of trigger factor.
• Co-crystallization of the trigger factor ribosome-binding domain with the Haloarcula marismortui large ribosomal subunit was performed.
• Structural analysis and domain mapping of trigger factor were conducted.

Main Results:

• The crystal structure reveals trigger factor adopts a unique "crouching dragon" conformation.
• Distinct domains (ribosome-binding tail, peptidyl-prolyl isomerase head, carboxy-terminal arms) were identified.
• Trigger factor's structure positions its domains over the ribosomal exit tunnel, creating a protected folding environment.

Conclusions:

• Trigger factor's unique structure facilitates co-translational protein folding by shielding nascent polypeptides.
• This shielding protects against proteases and aggregation.
• The findings suggest a novel mechanism of action for ribosome-associated chaperones in protein folding.