Short-Range Backbone Dihedral Rotations Modulate Internal Friction in Intrinsically Disordered Proteins

Area of Science:

• Biophysics
• Protein Dynamics
• Molecular Interactions

Background:

• Protein folding and dynamics are influenced by solvent viscosity and internal friction.
• Internal friction is the polypeptide chain's intrinsic resistance to conformational changes.
• The molecular origin of internal friction in intrinsically disordered proteins (IDPs) remains unclear.

Purpose of the Study:

• To investigate the molecular origin of internal friction in IDPs.
• To demonstrate that sequence-specific backbone dihedral barriers control local internal friction.
• To analyze the role of specific amino acids in modulating internal friction.

Main Methods:

• Site-directed fluorescence depolarization kinetics.
• Picosecond time-resolved fluorescence anisotropy measurements.
• Analysis of dihedral relaxation times using a linear viscosity-dependent model.

Main Results:

• Identified sequence-specific backbone dihedral barriers as the source of local internal friction.
• Observed low internal friction in nonproline segments and high internal friction in proline-containing segments.
• Demonstrated that glycine can compensate for the torsional stiffness introduced by proline.

Conclusions:

• Local internal friction in IDPs is governed by sequence-specific dihedral barriers.
• Amino acid sequence, particularly proline and glycine, plays a crucial role in modulating internal friction.
• Understanding local internal friction is key to comprehending IDP behavior in folding, binding, and assembly.