Protein chain collapse modulation and folding stimulation by GroEL-ES

Area of Science:

• Biochemistry
• Molecular Biology
• Protein Dynamics

Background:

• Polypeptide collapse is crucial for protein folding, aggregation, and phase separation.
• The role of cellular modulation of polypeptide collapse in controlling protein states remains largely unknown.

Purpose of the Study:

• To investigate whether the chaperonin GroEL-ES can modulate polypeptide collapse to accelerate protein folding.
• To elucidate the mechanisms by which GroEL-ES influences protein collapse and folding.

Main Methods:

• Integrated protein manipulation and live-cell imaging techniques were employed.
• The study focused on the effects of GroEL-ES on substrate protein collapse and folding transitions.

Main Results:

• Chaperonin GroEL-ES accelerates protein folding by strengthening polypeptide collapse.
• GroEL induces contractile forces, leading to substrate chain compaction and folding transitions within its cavity.
• Collapse enhancement is modulated by GroEL's nucleotide-bound states, GroES binding, and C-terminal tails.

Conclusions:

• Modulation of polypeptide collapse by GroEL-ES is a distinct mechanism for accelerating protein folding.
• This collapse modulation mechanism is likely broadly relevant to protein quality control machinery.
• The findings suggest a new perspective on the role of chaperonins in cellular proteostasis.