Nascent chains: folding and chaperone interaction during elongation on ribosomes

Area of Science:

• Molecular Biology
• Protein Folding
• Biochemistry

Background:

• Protein folding is crucial for cellular function.
• The timing and location of protein folding, particularly cotranslational folding on ribosomes, are not fully understood.
• Chaperone proteins assist in protein folding, but their role during nascent chain synthesis is an active area of research.

Purpose of the Study:

• To investigate whether nascent polypeptide chains can fold during their synthesis on ribosomes.
• To determine if protein folding occurs cotranslationally or post-translationally.
• To explore the interaction of nascent polypeptide chains with chaperones.

Main Methods:

• Utilized monoclonal antibodies specific for folding intermediates.
• Monitored the appearance of immunoreactive polypeptide chains during ribosomal synthesis.
• Studied bacteriophage P22 tail-spike protein and Escherichia coli tryptophan synthase beta-chains.
• Assessed the timing of immunoreactivity relative to polypeptide chain elongation.

Main Results:

• Identified nascent, immunoreactive chains of P22 tail-spike protein and E. coli tryptophan synthase beta-chains, suggesting cotranslational folding.
• Observed no delay in the appearance of immunoreactivity for intermediate-length tryptophan synthase beta-chains, supporting folding during elongation.
• Demonstrated interaction of newly synthesized, incomplete beta-chains with chaperones while still ribosome-bound.

Conclusions:

• Nascent polypeptide chains, including P22 tail-spike and tryptophan synthase beta-chains, can initiate folding on the ribosome.
• Chaperone association with nascent chains on the ribosome complicates the interpretation of folding status.
• Further investigation is needed to distinguish between true cotranslational folding and chaperone-mediated maintenance of an unfolded state.