How do surfactants unfold and refold proteins?

Area of Science:

• Biochemistry
• Structural Biology
• Physical Chemistry

Background:

• Sodium dodecyl sulfate (SDS) is a widely used anionic surfactant for protein denaturation.
• Controversy exists regarding the precise model of SDS-protein interactions, specifically "rod-like" structures.
• Existing models include the "core-shell" (protein-decorated micelles) and "beads-on-a-string" (micelles surrounding unfolded proteins).

Purpose of the Study:

• To definitively resolve the controversy surrounding SDS-protein interaction models.
• To elucidate the formation mechanism and structural characteristics of SDS-protein complexes.
• To investigate the reversibility of SDS-induced protein denaturation.

Main Methods:

• Calorimetry and small-angle X-ray scattering (SAXS) techniques.
• Advanced molecular dynamics simulations.
• Time-resolved SAXS and single-molecule studies.

Main Results:

• The study provides strong evidence favoring the "core-shell" model over the "beads-on-a-string" model.
• SDS-protein complex formation involves initial SDS binding, micelle growth by accretion, and asymmetric protein unfolding around micelles.
• Protein unfolding is complete at the tertiary level, and denaturation is generally reversible, except at low pH.

Conclusions:

• The "core-shell" model accurately describes SDS-protein interactions, clarifying decades of debate.
• The mechanism of SDS denaturation and refolding is now well-established.
• Future research can focus on variations with other ionic and biosurfactants.