Protein structure, activity and thermal stability within nanoscopic compartments

TL;DR

This study demonstrates that nanoscopic confinement of proteins within vesicles induces phase transitions and structural changes, significantly enhancing thermal stability and potentially aiding long-term storage and origins of life.

Contribution

It reveals how nanoscopic compartments induce phase transitions and structural modifications in proteins, improving stability and offering insights into early life preservation.

Findings

Protein confinement causes liquid-liquid phase transition.

Proteins exhibit non-alpha helical conformations within vesicles.

Thermal stability of proteins is significantly enhanced, up to 95°C.

Abstract

We report that protein confinement within nanoscopic vesicular compartments corresponds to a liquid-liquid phase transition with the protein/water within vesicle lumen interacting very differently than in bulk. We show this effect leads to considerable structural changes on the proteins with evidence suggesting non-alpha helical conformations. Most importantly both aspects lead to a significant improvement on protein stability against thermal denaturation up to 95degC at neutral pH, with little or no evidence of unfolding or reduced enzymatic activity. The latter parameter does indeed exhibit an increase after thermal cycling. Our results suggest that nanoscopic confinement is a promising new avenue for the enhanced long-term storage of proteins. Moreover, our investigations have potentially important implications for the origin of life, since such compartmentalization may well have been critical for ensuring the preservation of primordial functional proteins under relatively harsh conditions, thus playing a key role in the subsequent emergence of primitive life forms.