Variation of Structural and Dynamical Flexibility of Myelin Basic Protein in Response to Guanidinium Chloride

Area of Science:

• Biophysics
• Protein dynamics
• Structural biology

Background:

• Myelin basic protein (MBP) is a flexible, intrinsically disordered protein.
• Understanding protein response to denaturants is crucial for molecular biology.

Purpose of the Study:

• Investigate the structural and dynamic effects of guanidinium chloride (GndCl) on MBP.
• Characterize the relationship between MBP's structure and internal dynamics under varying GndCl concentrations.

Main Methods:

• Small-angle scattering (SAS) to probe overall protein structure.
• Neutron spin-echo spectroscopy (NSE) to analyze protein dynamics.
• Analysis using Zimm model with internal friction (ZIF) and normal mode (NM) analysis.

Main Results:

• 0.2 M GndCl induces charge screening, leading to a compact MBP conformation.
• Above 1 M GndCl, MBP undergoes structural expansion and swelling.
• Internal friction significantly contributes to dynamics in compact states, with a relaxation time of ~40 ns at high GndCl.
• NM analysis shows unaffected relaxation rates but increased motion amplitudes upon structural expansion.
• Brownian oscillator model suggests friction loss within MBP due to structural expansion.

Conclusions:

• MBP exhibits coupled structural and dynamical plasticity in response to GndCl.
• The behavior of MBP differs fundamentally from ideal polymers in solution.
• Denaturant-induced structural changes directly impact protein dynamics and internal friction.