Coupled folding and specific binding: fishing for amphiphilicity

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biophysics

Background:

• Proteins exhibit remarkable target selectivity and binding speed.
• Transcription factors bind specific DNA sequences rapidly, suggesting enhanced kinetics.
• Natively disordered protein structures facilitate cooperative folding and binding processes.

Purpose of the Study:

• To explore how protein intrinsically disordered structures contribute to rapid and selective target binding.
• To investigate the biological advantages of induced protein folding upon target recognition.
• To review experimental evidence for the 'fly-casting' mechanism in accelerating binding kinetics.

Main Methods:

• Review of experimental results in rationally designed peptide systems.
• Analysis of peptide systems where folding is coupled to amphiphilicity.
• Examination of peptide systems where folding is coupled to biomolecular activity.

Main Results:

• Disordered protein structures enable enhanced binding kinetics through cooperative folding.
• Induced folding provides plasticity for accommodating various target sizes and shapes.
• The 'fly-casting' effect, driven by induced folding, can overcome diffusion-limited binding rates.

Conclusions:

• Intrinsically disordered proteins utilize coupled folding and binding for efficient molecular recognition.
• Induced folding is a key mechanism for achieving rapid and selective protein-target interactions.
• Designed peptide systems serve as valuable models for understanding these biophysical principles.