Peripheral Protein Unfolding Drives Membrane Bending.

Area of Science:

• Biophysics
• Cell Biology
• Biochemistry

Background:

• Peripheral membrane proteins dynamically modulate lipid membrane curvature.
• Mechanisms include hydrophobic insertion, membrane scaffolding, and protein crowding-induced steric pressure.
• Intrinsically disordered proteins enhance crowding effects due to their large hydrodynamic radii.

Purpose of the Study:

• To investigate if the folding-unfolding transition of surface-bound proteins can trigger membrane bending.
• To explore protein unfolding as a novel mechanism for membrane deformation.

Main Methods:

• Utilized histidine-tagged human serum albumin (HSA) bound to Ni-NTA-DGS containing liposomes.
• Induced protein unfolding by reducing disulfide bonds.
• Observed membrane tubule formation using microscopy.

Main Results:

• Reduction of disulfide bonds led to HSA unfolding and subsequent membrane tubule formation.
• Tubule formation frequency was significantly higher when unfolded proteins were localized to phase-separated domains compared to fluid phases.
• Steric pressure generated by protein unfolding drives membrane deformation.

Conclusions:

• Protein conformational changes, specifically unfolding, can induce membrane curvature.
• This mechanism, driven by steric pressure from unfolding proteins, offers new insights into membrane dynamics.
• Findings are crucial for designing peripheral membrane protein immobilization strategies and understanding protein-driven membrane bending.