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The Effects of Pressure and Temperature on the Thermodynamics of α-Helices.

Makhatadze, G. I.; Moustouka, C.; Coffin, C.; Tzul, F. O.

2025-01-30 biophysics
10.1101/2025.01.29.635541 bioRxiv
Show abstract

In light of the recent realization that a large fraction of microbial biomass lives under high hydrostatic pressure, there is a renewed interest in understanding molecular details by which proteins in these organisms modulate their functional native state. The effects of pressure on protein stability are defined by the volume changes between native and denatured states. The conformational ensemble of the denatured state can depend on several extrinsic variables, such as pH and ionic strength of solvent, temperature, and pressure. The effect of the latter on the elements of the secondary structures, and -helical structures has been inconclusive. This has been largely due to the inherent difficulties of high-pressure experiments. Here, we adapted the method of choice, circular dichroism spectroscopy, on a well-established series of model peptides to study helical structure formation, while focusing on the pressure and temperature dependencies of the helix-coil transition. We find that at low temperatures, pressure stabilizes the helical structure, suggesting that the volume of the helix-coil transition is positive. However, at higher temperatures (>40{degrees}C), the volume changes become negative, and pressure destabilizes the helical structure.

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