Cotranslational folding--omnia mea mecum porto?

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Cotranslational folding, where proteins fold as they are synthesized, is crucial for cellular function.
• Molecular chaperones assist in protein folding but are involved in only a small fraction of cases.
• Recent advances in ribosomal structure provide insights into protein synthesis and folding mechanisms.

Purpose of the Study:

• To review evidence for cotranslational folding in prokaryotes and eukaryotes.
• To understand the role of the ribosome structure in nascent peptide folding.
• To hypothesize the location and timing of protein folding initiation.

Main Methods:

• Review of existing literature and evidence for cotranslational folding.
• Analysis of the crystal structure of the large ribosomal subunit (2.5 Å resolution).
• Examination of the ribosomal tunnel dimensions and properties.

Main Results:

• The nascent peptide traverses a ~100 Å tunnel within the ribosome.
• The tunnel's narrow diameter and properties likely prevent complex folding within most of its length.
• Nascent peptides within the ribosome range from 30 to 72 amino acids, exhibiting varied conformations.

Conclusions:

• Protein folding initiates within the ribosome's exit tunnel and continues on its surface.
• The distal part of the tunnel and a surface depression near the exit are proposed sites for folding.
• Cotranslational folding is a significant process, with the ribosome itself playing a role beyond mere synthesis.