Reduced Internal Friction by Osmolyte Interaction in Intrinsically Disordered Myelin Basic Protein

Area of Science:

• Biophysics
• Protein dynamics
• Neutron scattering

Background:

• Urea is a known osmolyte that denatures proteins by disrupting noncovalent bonds.
• Myelin basic protein (MBP) is an intrinsically disordered protein.
• Understanding protein denaturation is crucial for molecular biology and disease research.

Purpose of the Study:

• To investigate the structural and dynamic changes of myelin basic protein (MBP) upon urea-induced denaturation.
• To elucidate the role of urea in altering protein folding landscapes and internal friction.

Main Methods:

• Small-angle neutron scattering (SANS) to study protein structure.
• Neutron spin-echo spectroscopy (NSE) to probe protein dynamics.
• Analysis using the Zimm model including internal friction (ZIF).

Main Results:

• Urea-denatured MBP exhibits a more compact structure than ideal polymers, with complete loss of secondary structure.
• Internal motions in urea-denatured MBP are enhanced, characterized by increased relaxation time and motional amplitude.
• The internal friction parameter decreased significantly (by a factor of 6.5), indicating reduced energy barriers.

Conclusions:

• Urea significantly reduces internal friction and the global energy landscape depth of MBP.
• Denaturation by urea leads to a loss of restoring forces, allowing larger motional amplitudes.
• Urea-denatured MBP exhibits properties similar to synthetic polymers due to the elimination of noncovalent bonds.